Docosahexaenoic acid (DHA), a 22:6 n-3 polyunsaturated fatty acid, is the longest and most highly unsaturated fatty acid found in most membranes and has been shown to inhibit cancer cell growth in part by modifying cell signaling. In the current study, alterations to epidermal growth factor receptor (EGFR) signaling upon DHA supplementation are examined in A549 lung adenocarcinoma, WiDr colon carcinoma and MDA-MB-231 breast carcinoma cell lines. Interestingly, EGFR phosphorylation, most notably at the tyrosine 1068 residue, is dramatically upregulated, and EGFR association with the Sos1 guanine nucleotide exchange factor is concomitantly increased upon DHA supplementation. However, guanosine triphosphate-bound Ras and phosphorylated extracellular signal-regulated kinase (Erk)1/2 are paradoxically downregulated in the same treatments. Previous reports have noted changes in membrane microdomains upon DHA supplementation, and our findings confirmed that EGFR, but not Ras, is excluded from caveolin-rich lipid raft fractions in DHA-treated cells, resulting in a decreased association of Ras with Sos1 and the subsequent downregulation of Erk signaling. Xenografts of the A549 cell line implanted in athymic mice fed a control high-fat diet or a diet high in DHA confirmed our in vitro data. These results demonstrate for the first time a functional consequence of decreased EGFR protein in lipid raft microdomains as a result of DHA treatment in three different cancer models. In addition, we report the ability of DHA to enhance the efficacy of EGFR inhibitors on anchorage-independent cell growth (soft agar), providing evidence for the potential development of enhanced combination therapies.
The Drosophila stomatogastric nervous system (SNS) is a compact collection of neurons that arises from the migration of neural precursors. Here we describe genetic tools allowing functional analysis of the SNS during the migratory phase of development. We constructed GAL4 lines driven by fragments of the Ret promoter, which yielded expression in a subset of migrating neural SNS precursors and also included a distinct set of midgut associated cells. Screening of additional GAL4 lines driven by fragments of the Gfrl/Munin, forkhead, twist and goosecoid (Gsc) promoters identified a Gsc fragment with expression from initial selection of SNS precursors until the end of embryogenesis. Inhibition of EGFR signaling using three identified lines disrupted the correct patterning of the frontal and recurrent nerves. To manipulate the environment traveled by SNS precursors, a FasII-GAL4 line with strong expression throughout the entire intestinal tract was identified. The transgenic lines described offer the ability to specifically manipulate the migration of SNS precursors and will allow the modeling and in-depth analysis of neuronal migration in ENS disorders such as Hirschsprung’s disease.
Our objective was to determine the effects of feeding carinata meal (CRM) compared with distillers dried grains with solubles (DDGS) on growth performance, rumen fermentation, and nutrient utilization in peripubertal dairy heifers. A 16-wk randomized block design experiment with 24 Holstein heifers [6.6 ± 0.7 mo and 218 ± 27 kg of body weight (BW)] was conducted. Treatments diets were (1) 10% cold-pressed CRM and (2) 10% DDGS on a dry matter (DM) basis. The remainder of the diets consisted of grass hay, ground corn, soybean meal, and mineral mix. Diets were formulated to be isonitrogenous and isocaloric. Heifers were individually fed using a Calan gate feeding system, and the rations were limit-fed at 2.65% of BW on a DM basis to target a 0.8 kg/d of average daily gain. Heifers were weighed every 2 wk and the ration amount offered was adjusted accordingly. Frame sizes, BW, and body condition scores were measured 2 d every 2 wk throughout the study. During wk 12 and 16, rumen fluid samples were collected via esophageal tubing for pH, ammonia N, and volatile fatty acid analyses. In wk 16, fecal grab samples were collected for apparent total-tract digestibility estimation. Heifer DM intake, BW, average daily gain, and gain:feed were similar between treatments. No differences were observed between treatments in frame measurements or body condition scores. Rumen pH tended to be greater in CRM compared with DDGS. Rumen ammonia N and total volatile fatty acid concentration were not different between treatments. Apparent total-tract digestibility of DM, neutral detergent fiber, and acid detergent fiber were decreased in CRM compared with DDGS. A tendency was detected for reduced organic matter digestibility in CRM. No difference was observed between treatments for crude protein total-tract digestibility. However, these differences in total-tract nutrient digestibility were not large enough to influence growth performance. Overall, results demonstrated that growing heifers can be limit-fed diets with 10% CRM and maintain growth performance compared with a control diet containing 10% DDGS.
Most variables postulated by Andersen and Newman's model as being determinants for using health services were present in Costa Rica. Nevertheless, the significance of its factors varied between outpatient, hospitalisation and emergency services.
Characterizing the chemical properties of forage is critical for the production of improved pastures and livestock development. Conventional analysis methods are very time-and material-consuming, whereas near-infrared spectroscopy (NIRS) and chemometric analyses allow a fast simultaneous determination of various chemical or physical properties without the use of solvents or large sample amounts. The present research involved the development of models based on NIRS and partial least squares regression (PLS) to estimate the neutral detergent fiber (NDF), acid detergent fiber (ADF), cellulose, and crude protein (CP) contents in Brachiaria spp. forage samples. The models were constructed using spectral data in the range of 800 to 1850 nm. Different preprocessing methods were applied, such as standard normal variate and first-/second-derivative transformations. The obtained calibration models were internally cross-validated, displaying validation errors similar to those obtained for conventional methods. The predictive abilities of the developed models were evaluated for external set samples. NDF, ADF, cellulose, and CP contents were estimated with relative errors of prediction (REPs) of 1.8, 2.6, 4.1, and 8.5%, respectively. NIRS predictions are a useful and profitable tool for fast multi-sample chemical property analysis that is required for the assessment of forage quality. The obtained models are suitable for estimating the key chemical characteristics of forage quality. This research contributes a new approach to determining the quality of Brachiaria spp. forage and provides a new technological tool for the improvement of this crop.
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