Relationship among cattle breed and anabolic implant protocol relative to feedlot performance: Growth, temperament, feeding behavior, carcass traits, and economic return.

Recent research has suggested that different cattle breed types may respond differently to anabolic implant protocols of varying intensity. Therefore, the purpose of this research was to compare anabolic implant protocols in feedlot steers of 2 different breed types. Sixty steers were stratified by weight and breed in a 2 × 3 factorial design examining 2 different breeds: Angus (AN; n=38) or Santa Gertrudis influenced (SG; n=22), and 3 implant strategies: no implant (CON; n=20), a moderate intensity implant protocol (d0 implant: Revalor-G, d56 implant: Revalor-IS, d112 implant: Revalor-S; MI; n=20), or a high intensity implant protocol (d0 implant: Revalor-IS, d56 implant: Revalor-S, d112 implant: Revalor-200; HI; n=20). Steers were randomly placed into pens equipped with GrowSafe bunks to collect dry matter intake and feeding behavior. All animals were fed the same diet. Weight, chute score, exit velocity, serum, rectal temperature, hip height and 12th rib fat thickness were collected approximately every 28 d over a 196 d period. Serum urea nitrogen (SUN) was evaluated as well. Total average daily gain was increased (P < 0.0001) in both the HI and MI steers compared to the CON steers by 29.4% and 26%, respectively. A treatment × breed interaction was observed (P < 0.0001) for hip height, with AN-CON steers being shorter (P < 0.0007) than AN-HI, SG-CON, SG-MI, and SG-HI steers. A breed × treatment interaction was observed (P < 0.004) for chute score and rectal temperature, with SG-HI and SG-MI steers having increased chute scores (P < 0.001) when compared to AN-HI, AN-MI, AN-CON, and SG-CON throughout the course of the trial. Additionally, SG-HI and SG-MI steers had an increased rectal temperature (P < 0.004) compared to AN-HI, AN-MI, AN-CON, and SG-CON steers. A breed effect was observed (P = 0.002) for SUN with AN steers having increased (P = 0.002) SUN concentration compared to SG sired steers, in addition to a treatment effect (P < 0.0001), with CON steers having a higher (P < 0.0001) SUN concentration than MI and HI steers, regardless of breed. The MI implant protocol increased net return per head, on average, by $97.28, regardless of breed, while the HI implant protocol increased net return by only $80.84. Taken together, despite the cattle breed types responding differently to the different anabolic implant protocols at times, a moderate intensity anabolic implant protocol was optimal in this experiment for steers raised in a temperate climate.

Anabolic implants alter abundance of mRNA involved in muscle growth, metabolism, and inflammation in the longissimus of Angus steers in the feedlot.

The majority of beef cattle in the United States often receive at least one anabolic implant resulting in improved growth, feed efficiency, and environmental and economic sustainability. However, the physiological and molecular mechanisms through which anabolic implants increase skeletal muscle growth of beef cattle remain elusive. The objective of this study was to identify transcriptional changes occurring in skeletal muscle of steers receiving anabolic implants containing different steroid hormones. Forty-eight steers were stratified by weight into 1 of 4 (n = 12/treatment) implant treatment groups: (1) estradiol (ImpE2; 25.7 mg E2; Compudose, Elanco Animal Health, Greenfield, IN), (2) trenbolone acetate (ImpTBA; 200 mg TBA; Finaplix-H, Merck Animal Health, Madison, NJ), (3) combination (ImpETBA; 120 mg TBA + 24 mg E2; Revalor-S, Merck Animal Health), or (4) no implant (CON). Skeletal muscle biopsies were taken from the longissimus 2 and 10 d post-implantation. The mRNA abundance of 94 genes associated with skeletal muscle growth was examined. At 10 d post-implantation, steers receiving ImpETBA had greater (P = 0.02) myoblast differentiation factor 1 transcript abundance than CON. Citrate synthase abundance was increased (P = 0.04) in ImpETBA steers compared to CON steers. In ImpE2 steers 10 d post-implantation, muscle RING finger protein 1 decreased (P = 0.05) compared to CON steers, and forkhead box protein O4 decreased (P = 0.05) in ImpETBA steers compared to CON steers. Interleukin-6 abundance tended to be increased (P = 0.09) in ImpE2 steers compared to both ImpETBA and CON steers. Furthermore, interleukin-10 mRNA abundance tended to be increased (P = 0.06) in ImpTBA steers compared to ImpETBA steers. Leptin receptor abundance was reduced (P = 0.01) in both ImpE2 and ImpTBA steers when compared to CON steers. Abundance of phosphodiesterase 4B was increased (P = 0.04) in ImpTBA steers compared to CON steers 2 d post-implantation. Taken together, the results of this research demonstrate that estradiol increases skeletal muscle growth via pathways related to nutrient partitioning and mitochondria function, while trenbolone acetate improves steer skeletal muscle growth via pathways related to muscle growth.

Understanding the influence of trenbolone acetate and polyamines on proliferation of bovine satellite cells.

Approximately 90% of beef cattle on feed in the United States receive at least one anabolic implant, which results in increased growth, efficiency, and economic return to producers. However, the complete molecular mechanism through which anabolic implants function to improve skeletal muscle growth remains unknown. This study had 2 objectives: (1) determine the effect of polyamines and their precursors on proliferation rate in bovine satellite cells (BSC); and (2) understand whether trenbolone acetate (TBA), a testosterone analog, has an impact on the polyamine biosynthetic pathway. To address these, BSC were isolated from 3 finished steers and cultured. Once cultures reached 75% confluency, they were treated in 1% fetal bovine serum (FBS) and/or 10 nM TBA, 10 mM methionine (Met), 8 mM ornithine (Orn), 2 mM putrescine (Put), 1.5 mM spermidine (Spd), or 0.5 mM spermine (Spe). Initially, a range of physiologically relevant concentrations of Met, Orn, Put, Spd, and Spe were tested to determine experimental doses to implement the aforementioned experiments. One, 12, or 24 h after treatment, mRNA was isolated from cultures and abundance of paired box transcription factor 7 (Pax7), Sprouty 1 (Spry), mitogen-activated protein kinase-1 (Mapk), ornithine decarboxylase (Odc), and S adenosylmethionine (Amd1) were determined, and normalized to 18S. No treatment × time interactions were observed (P ≥ 0.05). Treatment with TBA, Met, Orn, Put, Spd, or Spe increased (P ≤ 0.05) BSC proliferation when compared with control cultures. Treatment of cultures with Orn or Met increased (P ≤ 0.01) expression of Odc 1 h after treatment when compared with control cultures. Abundance of Amd1 was increased (P < 0.01) 1 h after treatment in cultures treated with Spd or Spe when compared with 1% FBS controls. Cultures treated with TBA had increased (P < 0.01) abundance of Spry mRNA 12 h after treatment, as well as increased mRNA abundance of Mapk (P < 0.01) 12 h and 24 h after treatment when compared with 1% FBS control cultures. Treatment with Met increased (P < 0.01) mRNA abundance of Pax7 1 h after treatment as compared with 1% FBS controls. These results indicate that treatments of BSC cultures with polyamines and their precursors increase BSC proliferation rate, as well as abundance of mRNA involved in cell proliferation. In addition, treatment of BSC cultures with TBA, polyamines, or polyamine precursors impacts expression of genes related to the polyamine biosynthetic pathway and proliferation.

Laminarin-rich extract improves growth performance, small intestinal morphology, gene expression of nutrient transporters and the large intestinal microbial composition of piglets during the critical post-weaning period.

The identification of natural bioactive compounds which can prevent the post-weaning growth check and enhance gastrointestinal health in the absence of in-feed medications is an urgent priority for the swine industry. The objective of this experiment was to determine the effects of increasing dietary inclusion levels of laminarin in the first 14 d post-weaning on pig growth performance and weaning associated intestinal dysfunction. At weaning, ninety-six pigs (8·4 (sd 1·09) kg) (meatline boars × (large white × landrace sows)) were blocked by live weight, litter and sex and randomly assigned to: (1) basal diet; (2) basal + 100 parts per million (ppm) laminarin; (3) basal + 200 ppm laminarin and (4) basal + 300 ppm laminarin (three pigs/pen). The appropriate quantity of a laminarin-rich extract (65 % laminarin) was added to the basal diet to achieve the above dietary inclusion levels of laminarin. After 14 d of supplementation, eight pigs from the basal group and the best-performing laminarin group were euthanised for sample collection. The 300 ppm laminarin group was selected as this group had higher ADFI compared with all other groups and higher ADG than the basal group (P < 0·05). Laminarin supplementation increased villus height in the duodenum and jejunum (P < 0·05). Laminarin supplementation increased the expression of SLC2A8/GLUT8 in the duodenum, SLC2A2/GLUT2, SLC2A7/GLUT7, SLC15A1/PEPT1 and FABP2 in the jejunum and SLC16A1/MCT1 in the colon. Laminarin supplementation reduced Enterobacteriaceae numbers in the caecum (P < 0·05) and increased lactobacilli numbers (P < 0·05), total volatile fatty acid concentrations and the molar proportions of butyrate (P < 0·01) in the colon. In conclusion, 300 ppm laminarin from a laminarin-rich extract has potential, as a dietary supplement, to improve performance and prevent post-weaning intestinal dysfunction.

Women's alcohol consumption and cumulative incidence of live birth following in vitro fertilization.

OBJECTIVE: The objective of this study was to determine the effect of alcohol consumption on outcomes among women undergoing in vitro fertilization (IVF). DESIGN: This study is a retrospective cohort study. SETTING: This study was performed in a private academically affiliated IVF center. PATIENTS: Patients included women presenting for their first IVF cycle from July 2004 through October 2012. INTERVENTION: Women completed self-administered questionnaires before their first IVF cycle, which included report of usual alcohol consumption. Women were categorized as non-drinkers, social drinkers, or daily drinkers, as well as by the number of drinks consumed per week. Competing risks analysis was used to calculate the cumulative incidence of live birth after 6 cycles stratified by alcohol consumption. MAIN OUTCOME MEASURES: Main outcome measures included spontaneous abortion, clinical pregnancy, and live birth following IVF. RESULTS: There were 591 (27.7%) non-drinkers, 1466 (68.7%) social drinkers, and 77 (3.6%) daily drinkers (total n = 2134). In the first cycle, compared to non-drinkers, daily drinkers had a twofold increased risk of spontaneous abortion (adjusted risk ratio [aRR] 2.2; 95% confidence interval [CI] 1.1-4.5) among all cycle starts, and while their risk of live birth was 30% lower (aRR 0.7; 95% CI 0.4-1.3), the sample size was small, and it was not significantly lower. By the end of 6 cycles, social drinkers and daily drinkers did not differ from non-drinkers in their cumulative incidence of live birth (56.1, 50.6, and 52.1%, respectively; both P ≥ 0.28). CONCLUSION: There was a trend towards lower risk of live birth among daily drinkers. Daily drinkers had an increased risk of spontaneous abortion in the first cycle, but the number of daily drinkers was small.

Role of G protein-coupled estrogen receptor-1 in estradiol 17ß-induced alterations in protein synthesis and protein degradation rates in fused bovine satellite cell cultures.

In feedlot steers, estradiol-17ß (E2) and combined E2 and trenbolone acetate (a testosterone analog) implants enhance rate and efficiency of muscle growth; and, consequently, these compounds are widely used as growth promoters in several countries. Treatment with E2 stimulates protein synthesis rate and suppresses protein degradation rate in fused bovine satellite cell (BSC) cultures; however, the mechanisms involved in these effects are not known with certainty. Although the genomic effects of E2 mediated through the classical estrogen receptors have been characterized, recent studies indicate that binding of E2 to the G protein-coupled estrogen receptor (GPER)-1 mediates nongenomic effects of E2 on cellular function. Our current data show that inhibition of GPER-1, matrix metalloproteinases 2 and 9 (MMP2/9), or heparin binding epidermal growth factor-like growth factor (hbEGF) suppresses E2 stimulate protein synthesis rate in cultured BSCs (P < 0.001) suggesting that all of these are required in order for E2 to stimulate protein synthesis in these cultures. In contrast, inhibition of GPER-1, MMP2/9, or hbEGF has no effect on the ability of E2 to suppress protein degradation rates in fused BSC cultures indicating that these factors are not required in order for E2 to suppress protein degradation rate in these cells. Furthermore, treatment of fused BSC cultures with E2 increased (P < 0.05) pAKT levels indicating that the pAKT pathway may play a role in E2-stimulated effects on cultured BSC. In summary, our current data show that active GPER-1, MMP2/9, and hbEGF are necessary for E2-stimulated protein synthesis but not for E2-simulated suppression of protein degradation in cultured BSC. In addition, E2 treatment increases pAKT levels in cultured BSC.

Zinc methionine and laminarin have growth-enhancing properties in newly weaned pigs influencing both intestinal health and diarrhoea occurrence.

Three experiments were conducted to investigate the interaction between zinc methionine (ZnM) and laminarin (LAM) on piglet growth performance and intestinal health post-weaning. Experiment 1 was designed as 2 × 2 factorial with four treatments [n = 8, weaning age (WA) 24 days, live weight (LW) 7.15 kg]: (i) basal diet (BD); (ii) BD + 500 mg/kg ZnM; (iii) BD + 300 mg/kg LAM; and (iv) BD + 500 mg/kg ZnM + 300 mg/kg LAM. There was an interaction (p < 0.05) between LAM and ZnM. Pigs that were offered the LAM diet had a similar performance to the BD. However, when combining LAM with ZnM, pigs had reduced average daily gain (ADG), gain-to-feed ratio (G:F) and LW at slaughter at day 8 post-weaning compared to the ZnM. Both LAM and ZnM improved the small intestinal morphology of the pigs at day 8 post-weaning. Experiment 2 was designed as 2 × 2 factorial with four dietary treatments (n = 9, WA 24 days, LW 7.32 kg): (i) BD; (ii) BD + 500 mg/kg ZnM; (iii) BD + 175 mg/kg LAM; and (iv) BD + 500 mg/kg ZnM + 175 mg/kg LAM. The ADG and average daily feed intake were improved between day 0 and 31 PW when pigs were offered a LAM diet (p < 0.01). Faecal scores were reduced between day 0 and day 31 post-weaning with ZnM (p < 0.001). Experiment 3 consisted of four dietary treatments (n = 10, WA 24 days, LW 7.32 kg): (i) BD; (ii) BD + 3300 mg/kg zinc oxide (ZnO); (iii) BD + 500 mg/kg ZnM; and (iv) BD + 175 mg/kg LAM. Pigs that were offered the ZnO diet had an increased ADG compared to the BD or ZnM diets (p < 0.01). Pigs that were offered the LAM diet had increased ADG compared to the ZnM diet (p < 0.05). Faecal scores were reduced between day 0 and day 31 PW with ZnM or ZnO supplementation (p < 0.001). In conclusion, the inclusion of 175 mg/kg LAM and ZnO improved ADG while both ZnO and ZnM reduced the faecal scores post-weaning.

Active G protein-coupled receptors (GPCR), matrix metalloproteinases 2/9 (MMP2/9), heparin-binding epidermal growth factor (hbEGF), epidermal growth factor receptor (EGFR), erbB2, and insulin-like growth factor 1 receptor (IGF-1R) are necessary for trenbolone acetate-induced alterations in protein turnover rate of fused bovine satellite cell cultures.

Trenbolone acetate (TBA), a testosterone analog, increases protein synthesis and decreases protein degradation in fused bovine satellite cell (BSC) cultures. However, the mechanism through which TBA alters these processes remains unknown. Recent studies indicate that androgens improve rate and extent of muscle growth through a nongenomic mechanism involving G protein-coupled receptors (GPCR), matrix metalloproteinases (MMP), heparin-binding epidermal growth factor (hbEGF), the epidermal growth factor receptor (EGFR), erbB2, and the insulin-like growth factor-1 receptor (IGF-1R). We hypothesized that TBA activates GPCR, resulting in activation of MMP2/9 that releases hbEGF, which activates the EGFR and/or erbB2. To determine whether the proposed nongenomic pathway is involved in TBA-mediated alterations in protein turnover, fused BSC cultures were treated with TBA in the presence or absence of inhibitors for GPCR, MMP2/9, hbEGF, EGFR, erbB2, or IGF-1R, and resultant protein synthesis and degradation rates were analyzed. Assays were replicated at least 9 times for each inhibitor experiment utilizing BSC cultures obtained from at least 3 different steers that had no previous exposure to steroid compounds. As expected, fused BSC cultures treated with 10 n TBA exhibited increased ( < 0.05) protein synthesis rates and decreased ( < 0.05) protein degradation rates when compared to control cultures. Treatment of fused BSC cultures with 10 n TBA in the presence of inhibitors for GPCR, MMP2/9, hbEGF, EGFR, erbB2, or IGF-1R suppressed ( < 0.05) TBA-mediated increases in protein synthesis rate. Alternatively, inhibition of GPCR, MMP2/9, hbEGF, EGFR, erbB2, or IGF-1R in the presence of 10 n TBA each had no ( > 0.05) effect on TBA-mediated decreases in protein degradation. However, inhibition of both EGFR and erbB2 in the presence of 10 n TBA resulted in decreased ( < 0.05) ability of TBA to decrease protein degradation rate. Additionally, fused BSC cultures treated with 10 n TBA exhibit increased ( < 0.05) pAKT protein levels. These data indicate the TBA-mediated increases in protein synthesis likely involve GPCR, MMP2/9, hbEGF, EGFR, erbB2, and IGF-1R. However, the mechanism through which TBA mediates changes in protein degradation is different and appears to involve only the EGFR and erbB2. Furthermore, it appears the protein kinase B pathway is involved in TBA's effects on fused BSC cultures.

Investigating the Swimming of Microbial Pathogens Using Digital Holography.

To understand much of the behaviour of microbial pathogens, it is necessary to image living cells, their interactions with each other and with host cells. Species such as Escherichia coli are difficult subjects to image: they are typically microscopic, colourless and transparent. Traditional cell visualisation techniques such as fluorescent tagging or phase-contrast microscopy give excellent information on cell behaviour in two dimensions, but no information about cells moving in three dimensions. We review the use of digital holographic microscopy for three-dimensional imaging at high speeds, and demonstrate its use for capturing the shape and swimming behaviour of three important model pathogens: E. coli, Plasmodium spp. and Leishmania spp.

The effect of algal polysaccharides laminarin and fucoidan on colonic pathology, cytokine gene expression and Enterobacteriaceae in a dextran sodium sulfate-challenged porcine model.

The algal polysaccharides laminarin (LAM) and fucoidan (FUC) have potent anti-inflammatory activities in the gastrointestinal tract. Our objective was to examine the impact of prior consumption of LAM and/or FUC on pathology and inflammation following a dextran sodium sulfate (DSS) challenge in pigs. Pigs (n 7/group) were assigned to one of five experimental groups for 56 d. From 49-55 d, distilled water or DSS was administered intragastrically. The experimental groups were: (1) basal diet + distilled water (control); (2) basal diet + DSS (DSS); (3) basal diet + FUC + DSS (FUC + DSS); (4) basal diet + LAM + DSS (LAM + DSS); and (5) basal diet + LAM + FUC + DSS (LAMFUC + DSS). The DSS group had decreased body-weight gain (P < 0·05) and serum xylose (P < 0·05), and increased proximal colon pathology score (P < 0·05), diarrhoeal score (P < 0·001) and colonic Enterobacteriaceae (P < 0·05) relative to the control group. The FUC + DSS (P < 0·01), LAM + DSS (P < 0·05) and LAMFUC + DSS (P < 0·05) groups had improved diarrhoeal score, and the LAMFUC + DSS (P < 0·05) group had improved body weight relative to the DSS group. The FUC + DSS group (P < 0·001), LAM + DSS group (P < 0·05) and LAMFUC + DSS group (P < 0·001) had lower IL-6 mRNA abundance relative to the DSS group. The LAM + DSS group had reduced Enterobacteriaceae in proximal colon digesta relative to the DSS group (P < 0·05). In conclusion, FUC or a combination of FUC and LAM improved body-weight loss, diarrhoeal scores and clinical variables associated with a DSS challenge in pigs, in tandem with a reduction in colonic IL-6 mRNA abundance.

Maternal supplementation of seaweed-derived polysaccharides improves intestinal health and immune status of suckling piglets.

The experiment investigated the effect of maternal dietary supplementation of seaweed-derived polysaccharides (SDP) (-SDP v. +SDP, n   20) from day 83 of gestation until weaning (day 28) on selected sow faeces and piglet digesta microbiota populations, piglet small-intestinal morphology, and intestinal nutrient transporter and inflammatory cytokine gene expression at birth, 48 h after birth and weaning. The effect of maternal dietary treatment on the piglet gene expression profile of inflammatory cytokines in the colon following a lipopolysaccharide (LPS) challenge was also investigated. Dietary SDP reduced sow faecal Enterobacteriaceae gene numbers at parturition. Small-intestinal morphology, nutrient transporter and cytokine gene expression in newborn piglets did not differ between maternal dietary treatments (P > 0·10). At 48 h after birth, sodium-glucose-linked transporter 1 gene expression was down-regulated in the ileum of piglets suckling the SDP-supplemented sows compared with those suckling the basal sows (P = 0·050). There was a SDP × LPS challenge interaction on IL-1 and IL-6 gene expression in the colon of piglets (P < 0·05). The gene expression of IL-1 and IL-6 was down-regulated in the LPS-challenged colon of piglets suckling the SDP sows compared with those suckling the basal sows (P < 0·05). However, there was no difference in IL-1 and IL-6 gene expression in the unchallenged colon between treatment groups. At weaning, piglets suckling the SDP-supplemented sows had increased villus height in the jejunum and ileum compared with those suckling the basal-fed sows (P < 0·05). In conclusion, maternal dietary SDP supplementation enhanced the immune response of suckling piglets and improved gut morphology, making them more immune competent to deal with post-weaning adversities.

Role of G protein-coupled receptors (GPCR), matrix metalloproteinases 2 and 9 (MMP2 and MMP9), heparin-binding epidermal growth factor-like growth factor (hbEGF), epidermal growth factor receptor (EGFR), erbB2, and insulin-like growth factor 1 receptor (IGF-1R) in trenbolone acetate-stimulated bovine satellite cell proliferation.

Implanting cattle with steroids significantly enhances feed efficiency, rate of gain, and muscle growth. However, the mechanisms responsible for these improvements in muscle growth have not been fully elucidated. Trenbolone acetate (TBA), a testosterone analog, has been shown to increase proliferation rate in bovine satellite cell (BSC) cultures. The classical genomic actions of testosterone have been well characterized; however, our results indicate that TBA may also initiate a quicker, nongenomic response that involves activation of G protein-coupled receptors (GPCR) resulting in activation of matrix metalloproteinases 2 and 9 (MMP2 and MMP9) that release membrane-bound heparin-binding epidermal growth factor-like growth factor (hbEGF), which then binds to and activates the epidermal growth factor receptor (EGFR) and/or erbB2. Furthermore, the EGFR has been shown to regulate expression of the IGF-1 receptor (IGF-1R), which is well known for its role in modulating muscle growth. To determine whether this nongenomic pathway is potentially involved in TBA-stimulated BSC proliferation, we analyzed the effects of treating BSC with guanosine 5'-O-2-thiodiphosphate (GDPßS), an inhibitor of all GPCR; a MMP2 and MMP9 inhibitor (MMPI); CRM19, a specific inhibitor of hbEGF; AG1478, a specific EGFR tyrosine kinase inhibitor; AG879, a specific erbB2 kinase inhibitor; and AG1024, an IGF-1R tyrosine kinase inhibitor on TBA-stimulated proliferation rate (H-thymidine incorporation). Assays were replicated at least 9 times for each inhibitor experiment using BSC cultures obtained from at least 3 different animals. Bovine satellite cell cultures were obtained from yearling steers that had no previous exposure to androgenic or estrogenic compounds. As expected, BSC cultures treated with 10 n TBA showed ( < 0.05) increased proliferation rate when compared with control cultures. Additionally, treatment with 5 ng hbEGF/mL stimulated proliferation in BSC cultures ( < 0.05). Treatment with GDPßS, MMPI, CRM197, AG1024, AG1478, and/or AG879 all suppressed ( < 0.05) TBA-induced increases in proliferation. These data indicate that TBA likely initiates a nongenomic response involving GPCR, MMP2 and MMP9, hbEGF, EGFR, erbB2, and IGF-1R, which may play a role in TBA-mediated increases in BSC proliferation.

Phase-field crystal model for a diamond-cubic structure.

We present a structural phase-field crystal model [M. Greenwood et al., Phys. Rev. Lett. 105, 045702 (2010)] that yields a stable dc structure. The stabilization of a dc structure is accomplished by constructing a two-body direct correlation function (DCF) approximated by a combination of two Gaussian functions in Fourier space. A phase diagram containing a dc-liquid phase coexistence region is calculated for this model. We examine the energies of solid-liquid interfaces with normals along the [100], [110], and [111] directions. The dependence of the interfacial energy on a temperature parameter, which controls the heights of the peaks in the two-body DCF, is described by a Gaussian function. Furthermore, the dependence of the interfacial energy on the peak widths of the two-body DCF, which controls the excess energy associated with interfaces, defects, and strain, is described by an inverse power law. These relationships can be used to parametrize the phase-field crystal model for the dc structure to match solid-liquid interfacial energies to those measured experimentally or calculated from atomistic simulations.

Effects of dietary potato by-product and rumen-protected histidine on growth, carcass characteristics and quality attributes of beef.

We hypothesized that variable composition in finishing rations, more specifically; the proportion of potato-by-product (PBP) and rumen protected histidine (His) supplementation may influence growth and meat quality attributes. Two different diets were fed (1) finishing ration with corn and barley as grains (CB, n = 20) and (2) substitution of 10% corn, DM basis, with PBP (PBP, n = 20). Additionally, half of each dietary treatment received 50 g/hd/d rumen protected His (HS, n= 20) while the other half received no supplement (NS, n = 20). Inclusion of 10% PBP or HS did not affect growth or carcass traits. Color stability was analyzed using Hunter color values as well as AMSA visual appraisal in both longissimus thoracis (LT) and gluteus medius (GM) muscles. The LT, but not the GM, of CB steers was more color stable over a 9 d simulated retail display compared to those fed a PB diet. Steers receiving HS produced significantly (P < 0.05) more color stable LT and GM steaks.

Role of G protein-coupled estrogen receptor-1, matrix metalloproteinases 2 and 9, and heparin binding epidermal growth factor-like growth factor in estradiol-17ß-stimulated bovine satellite cell proliferation.

In feedlot steers, estradiol-17ß (E2) and combined E2 and trenbolone acetate (a testosterone analog) implants enhance rate and efficiency of muscle growth; and, consequently, these compounds are widely used as growth promoters. Although the positive effects of E2 on rate and efficiency of bovine muscle growth are well established, the mechanisms involved in these effects are not well understood. Combined E2 and trenbolone acetate implants result in significantly increased muscle satellite cell number in feedlot steers. Additionally, E2 treatment stimulates proliferation of cultured bovine satellite cells (BSC). Studies in nonmuscle cells have shown that binding of E2 to G protein-coupled estrogen receptor (GPER)-1 results in activation of matrix metalloproteinases 2 and 9 (MMP2/9) resulting in proteolytic release of heparin binding epidermal growth factor-like growth factor (hbEGF) from the cell surface. Released hbEGF binds to and activates the epidermal growth factor receptor resulting in increased proliferation. To assess if GPER-1, MMP2/9, and/or hbEGF are involved in the mechanism of E2-stimulated BSC proliferation, we have examined the effects of G36 (a specific inhibitor of GPER-1), CRM197 (a specific inhibitor of hbEGF), and MMP-2/MMP-9 Inhibitor II (an inhibitor of MMP2/9 activity) on E2-stimulated BSC proliferation. Inhibition of GPER-1, MMP2/9, or hbEGF suppresses E2-stimulated BSC proliferation (P < 0.001) suggesting that all these are required in order for E2 to stimulate BSC proliferation. These results strongly suggest that E2 may stimulate BSC proliferation by binding to GPER-1 resulting in MMP2/9-catalyzed release of cell membrane-bound hbEGF and subsequent activation of epidermal growth factor receptor by binding of released hbEGF.

Dynamics of coarsening in multicomponent lipid vesicles with non-uniform mechanical properties.

Multicomponent lipid vesicles are commonly used as a model system for the complex plasma membrane. One phenomenon that is studied using such model systems is phase separation. Vesicles composed of simple lipid mixtures can phase-separate into liquid-ordered and liquid-disordered phases, and since these phases can have different mechanical properties, this separation can lead to changes in the shape of the vesicle. In this work, we investigate the dynamics of phase separation in multicomponent lipid vesicles, using a model that couples composition to mechanical properties such as bending rigidity and spontaneous curvature. The model allows the vesicle surface to deform while conserving surface area and composition. For vesicles initialized as spheres, we study the effects of phase fraction and spontaneous curvature. We additionally initialize two systems with elongated, spheroidal shapes. Dynamic behavior is contrasted in systems where only one phase has a spontaneous curvature similar to the overall vesicle surface curvature and systems where the spontaneous curvatures of both phases are similar to the overall curvature. The bending energy contribution is typically found to slow the dynamics by stabilizing configurations with multiple domains. Such multiple-domain configurations are found more often in vesicles with spheroidal shapes than in nearly spherical vesicles.

An examination of the association of serum IGF-I concentration, potential candidate genes, and fiber type composition with variation in residual feed intake in progeny of Red Angus sires divergent for maintenance energy EPD.

Investigating the genetic and physiological drivers of postweaning residual feed intake (RFI) and finishing phase feed efficiency (FE) may identify underlying mechanisms that are responsible for the variation in these complex FE traits. The objectives were 1) to evaluate the relationship of serum IGF-I concentration and muscle gene expression with postweaning RFI and sire maintenance energy (MEM) EPD and 2) to determine fiber type composition as it relates to postweaning RFI and finishing phase FE. Results indicate that RFI and serum IGF-I concentration were not associated (P > 0.05); however, negative correlations (P < 0.05) between sire MEM EPD and serum IGF-I concentration were observed. Gene expression differences between high- and low-RFI animals were observed in cohort 1, where IGFBP5 expression was greater (P < 0.05) in high-RFI animals. When animals were grouped according to sire MEM EPD, the low MEM EPD group of cohort 1 showed greater muscle mRNA expression (P < 0.01) of fatty acid synthase (FASN) and marginally (P < 0.10) greater expression of IGFBP5 and C/EBP alpha (C/EBPα) whereas the high MEM EPD group of cohort 2 had greater muscle mRNA expression of IGFBP2 (P < 0.05) and C/EBPα (P ≤ 0.01) and marginally (P < 0.10) greater expression of IGFBP3. Biopsy tissue samples collected at harvest revealed that the percentage of type IIa fibers was lower (P ≤ 0.05) in high-RFI steers, with a similar trend (P < 0.10) being observed in high finishing phase FE steers. The percentage of type IIb fibers was higher (P < 0.05) in high-RFI (and finishing phase FE) steers than in low-RFI (and finishing phase FE) steers. There was a marginal, negative correlation between RFI and type I (r = -0.36, P = 0.08) and IIa (r = -0.37, P = 0.07) fiber percentages and a positive correlation (r = 0.48, P = 0.01) between RFI and type IIb fiber percentage whereas finishing phase FE was negatively correlated (r = -0.43, P = 0.03) with type I fiber percentage and positively correlated (r = 0.44, P = 0.03) with type IIb fiber percentage. Therefore, our data indicate that 1) serum IGF-I (collected at weaning) is not an indicator of postweaning RFI, 2) the GH-IGF axis appears to have some involvement with RFI at the molecular level; however, muscle gene expression results were not consistent across cohorts, and 3) low-RFI animals may have the ability to more efficiently maintain and accrete muscle mass due to their fiber type composition, specifically a greater proportion of type I fibers.

Classical density functional theory and the phase-field crystal method using a rational function to describe the two-body direct correlation function.

We introduce a new approach to represent a two-body direct correlation function (DCF) in order to alleviate the computational demand of classical density functional theory (CDFT) and enhance the predictive capability of the phase-field crystal (PFC) method. The approach utilizes a rational function fit (RFF) to approximate the two-body DCF in Fourier space. We use the RFF to show that short-wavelength contributions of the two-body DCF play an important role in determining the thermodynamic properties of materials. We further show that using the RFF to empirically parametrize the two-body DCF allows us to obtain the thermodynamic properties of solids and liquids that agree with the results of CDFT simulations with the full two-body DCF without incurring significant computational costs. In addition, the RFF can also be used to improve the representation of the two-body DCF in the PFC method. Last, the RFF allows for a real-space reformulation of the CDFT and PFC method, which enables descriptions of nonperiodic systems and the use of nonuniform and adaptive grids.

A dose-finding study of temsirolimus and liposomal doxorubicin for patients with recurrent and refractory bone and soft tissue sarcoma.

There are few effective therapies for high-risk sarcomas. Initial chemosensitivity is often followed by relapse. In vitro, mammalian target of rapamycin (mTOR) inhibition potentiates the efficacy of chemotherapy on resistant sarcoma cells. Although sarcoma trials using mTOR inhibitors have been disappointing, these drugs were used as maintenance. We conducted a Phase I/II clinical trial to test the ability of temsirolimus to potentiate the cytotoxic effect of liposomal doxorubicin and present here the dose-finding portion of this study. Adult and pediatric patients with recurrent or refractory sarcomas were treated with increasing doses of liposomal doxorubicin and temsirolimus using a continual reassessment method for escalation, targeting a dose-limiting toxicity rate of 20%. Blood samples were drawn before and after the first dose of temsirolimus in Cycles 1 and 2 for pharmacokinetic analysis. The maximally tolerated dose combination was liposomal doxorubicin 30 mg/m(2) monthly with temsirolimus 20 mg/m(2) weekly. Hematologic toxicity was common but manageable. Dose-limiting toxicities were primarily renal. Concurrent administration of liposomal doxorubicin resulted in increased exposure to sirolimus, the active metabolite of temsirolimus. Thus, the combination of liposomal doxorubicin and temsirolimus is safe for heavily pretreated sarcoma patients. Co-administration with liposomal doxorubicin did not alter temsirolimus pharmacokinetics, but increased exposure to its active metabolite.