The ileal and total tract digestibility fibre and nutrients in pigs fed high-fibre cereal-based diets provided without and with a carbohydrase complex.

The effect of carbohydrase can be variable according to the complexity of cereal grains and co-products. Studies on the effect of carbohydrase on cereal diets varying in complexity are scarce. This study was conducted to investigate the apparent ileal (AID) and total tract digestibility (ATTD) of energy, fibre and nutrients in pigs fed diets based on cereal grains and co-products without and with supplementation with a carbohydrase complex in the form of xylanase, arabinofuranosidase and ß-glucanase. The experiment was carried out as an 8 × 4 Youden Square design (eight diets and four periods by two blocks) using 16 growing pigs (33.3 ± 0.8 kg) surgically fitted with a T-cannula in the terminal ileum. The pigs were fed eight experimental diets based on either - maize, wheat, rye, or a wheat and rye mix that were provided with or without enzyme supplementation. The AID and ATTD of DM, organic matter, energy, CP, fat, starch, and soluble and insoluble non-starch polysaccharides (NSPs) were studied using titanium dioxide as an indigestible marker. There was a cereal type effect (P < 0.05) of the AID of most of the nutrients investigated but ash and NSP and some of its constituents but with no interactions between cereal types and carbohydrase supplementation (P > 0.05). The ATTD of nutrients in the large intestine was mainly influenced by the fibre composition and was significantly lower (P < 0.001) for NSP, protein and energy for the Maize than the other diets. Supplementation of the cereal diets with the carbohydrase complex partially degrades arabinoxylan (AX) and ß-glucan giving rise to a generally higher AID of high-molecular weight arabinoxylan (P = 0.044), starch (P = 0.042), a tendency (P < 0.10) of higher AID of non-cellulosic polysaccharide glucose residue (ß-glucan) and soluble arabinoxylan (AX) whereas none of the other components were affected (P > 0.05). Collectively, the results indicate that the carbohydrase complex degrades AX in the stomach and small intestine, leading to a higher AID but with no influence on the ATTD of fibres, nutrients, and energy.

Influence of dietary fibre on nutrient digestibility and energy utilisation in growing pigs fed diets varying in soluble and insoluble fibres from co-products.

The co-products from the industry are used to reduce costs in pig diets. However, the co-products used in pig diets are limited because of a high fibre content which is not digested by endogenous enzymes and is resistant to degradation in the small and large intestines. The aim of this study was to investigate digestibility of nutrients and energy, and energy utilisation in pigs fed diets with various soluble and insoluble dietary fibre (DF) from co-products. The experiment was performed as a 4 × 4 Latin square design (four diets and four periods) using four growing pigs (66.2 ±â€¯7.8 kg) surgically fitted with a T-cannula in the end of the small intestine. The pigs were fed four experimental diets: low-fibre control (LF), high-fibre control (HF), high-soluble fibre (HFS) and high-insoluble fibre (HFI) diets. The apparent ileal digestibility (AID) and apparent total tract digestibility (ATTD) of ash, organic matter, CP, fat, carbohydrates, starch and non-starch polysaccharides (NSP) divided into cellulose and soluble and insoluble non-cellulosic polysaccharide residues were measured using chromic oxide as marker. The recovery of total solid materials, organic matter and total carbohydrates in ileal digesta in pigs fed the HF and HFS diets was higher than in pigs fed LF and HFI, whereas recovery of organic matter and total carbohydrates in faecal materials in the HFS diet was lowest (P < 0.05). AID of organic matter, total carbohydrates and starch was lowest for HFS diet (P < 0.05). ATTD of organic matter and CP was higher for LF diet compared with other diets (P < 0.05), whereas total NSP, cellulose and non-cellulosic polysaccharides residues were highest for HFS diet (P < 0.05). Lactic acid in ileal digesta was influenced by dietary composition (P < 0.05) whereas neither type nor level of DF affected short chain fatty acids. The digestible energy, metabolisable energy, net energy and retained energy intake were similar among diets without influence of DF inclusion (P > 0.05). The metabolisable energy:digestible energy ratio was lower when feeding the HFS diet because of a higher fermentative methane loss. Faecal nitrogen and carbon were positively correlated with DM intake and insoluble DF in the diets (P < 0.05), but nitrogen and carbon (% of intake) were similar among diets. The present findings suggest that high-DF co-products can be used as ingredients of pig diets when features of DF are considered.

Carbohydrase Complexes Rich in Xylanases and Arabinofuranosidases Affect the Autofluorescence Signal and Liberate Phenolic Acids from the Cell Wall Matrix in Wheat, Maize, and Rice Bran: An In Vitro Digestion Study.

The high fiber content of cereal coproducts used in animal feed reduces the digestibility and nutrient availability. Therefore, the aim of this study was to elucidate the ability of two carbohydrase complexes to degrade the cell wall of wheat, maize, and rice during in vitro digestion. One complex was rich in cell-wall-degrading enzymes (NSPase 1), and the other was similar but additionally enriched with xylanases and arabinofuranosidases (NSPase 2). Degradation of arabinoxylan, the main cereal cell wall polysaccharide, was followed directly by gas-liquid chromatography (GLC) and indirectly through phenolic acid liberation as quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The effect was additionally visualized using a unique multispectral autofluorescence approach. Wheat fractions, in particular aleurone, were susceptible to degradation as judged from the redistribution of arabinoxylan (25% reduction in insoluble arabinoxylan), whereas the highest relative liberation of ferulic acid was observed in rice bran (6%). All cereal fractions, except for maize, had a higher release of ferulic acid with NSPase 2 than NSPase 1 (38% in rice and wheat bran, 30% in wheat whole grain, and 28% in wheat aleurone). Thus, the carbohydrase complexes were able to degrade important cell wall components during in vitro digestion but apparently through different mechanisms in wheat, maize, and rice.

Urine Extracellular Vesicle GATA2 mRNA Discriminates Biopsy Result in Men with Suspicion of Prostate Cancer.

PURPOSE: Prostate specific antigen has limited performance in detecting prostate cancer. The transcription factor GATA2 is expressed in aggressive prostate cancer. We analyzed the predictive value of urine extracellular vesicle GATA2 mRNA alone and in combination with a multigene panel to improve detection of prostate cancer and high risk disease. MATERIALS AND METHODS: GATA2 mRNA was analyzed in matched extracellular vesicles isolated from urines before and after prostatectomy (16) and paired urine and tissue prostatectomy samples (19). Extracellular vesicle GATA2 mRNA performance to distinguish prostate cancer and high grade disease was tested in training (52) and validation (165) cohorts. The predictive value of a multigene score including GATA2, PCA3 and TMPRSS2-ERG (GAPT-E) was tested in both cohorts. RESULTS: Confirming its prostate origin, urine extracellular vesicle GATA2 mRNA levels decreased significantly after prostatectomy and correlated with prostate cancer tissue GATA2 mRNA levels. In the training and validation cohort GATA2 discriminated prostate cancer (AUC 0.74 and 0.66) and high grade disease (AUC 0.78 and 0.65), respectively. Notably, the GAPT-E score improved discrimination of prostate cancer (AUC 0.84 and 0.72) and high grade cancer (AUC 0.85 and 0.71) in both cohorts when compared with each biomarker alone and PT-E (PCA3 and TMPRSS2-ERG). A GAPT-E score for high grade prostate cancer would avoid 92.1% of unnecessary prostate biopsies, compared to 61.9% when a PT-E score is used. CONCLUSIONS: Urine extracellular vesicle GATA2 mRNA analysis improves the detection of high risk prostate cancer and may reduce the number of unnecessary biopsies.

Increasing levels of rapeseed expeller meal in diets for pigs: effects on protein and energy metabolism.

The heavy reliance on imported soybean meal (SBM) as a protein source makes it necessary for the European pig industry to search for alternatives and to develop pigs that perform efficiently when fed such ingredients. Digestion and metabolism are major physiological processes contributing to variation in feed efficiency. Therefore, an experiment was conducted to assess the effects of replacing SBM with increasing levels of rapeseed meal (RSM) in diets for young pigs on apparent total tract digestibility (ATTD) of energy and nutrients, nitrogen (N) balance, energy metabolism and carbohydrate, protein and fat oxidation. Four diets were fed to 32 pigs (22.7±4.1 kg initial BW) for three weeks. The diets consisted of a control cereal grain-SBM basal diet and three test diets where SBM and wheat were partially replaced with 10%, 20%, and 30% of expeller RSM. Increasing level of RSM in the diets linearly reduced ATTD of organic matter, CP, total carbohydrates, dietary fiber and energy. Utilization of digested nitrogen (DN) for N retention and total N excretion were not affected by RSM inclusion, however, RSM inclusion induced a shift in N excretion from urine to feces. Despite a linear increase in liver to metabolic BW ratio, heat production and utilization of metabolizable energy (ME) for retention were not affected by increasing RSM inclusion. In conclusion, replacing SBM with up to 30% of expeller RSM in nutritionally balanced diets for young pigs reduced the ATTD of most nutrients and energy, but did not affect N and energy retention in the body or efficiency of utilization of DN or ME for retention.

Cell cycle-coupled expansion of AR activity promotes cancer progression.

The androgen receptor (AR) is required for prostate cancer (PCa) survival and progression, and ablation of AR activity is the first line of therapeutic intervention for disseminated disease. While initially effective, recurrent tumors ultimately arise for which there is no durable cure. Despite the dependence of PCa on AR activity throughout the course of disease, delineation of the AR-dependent transcriptional network that governs disease progression remains elusive, and the function of AR in mitotically active cells is not well understood. Analyzing AR activity as a function of cell cycle revealed an unexpected and highly expanded repertoire of AR-regulated gene networks in actively cycling cells. New AR functions segregated into two major clusters: those that are specific to cycling cells and retained throughout the mitotic cell cycle ('Cell Cycle Common'), versus those that were specifically enriched in a subset of cell cycle phases ('Phase Restricted'). Further analyses identified previously unrecognized AR functions in major pathways associated with clinical PCa progression. Illustrating the impact of these unmasked AR-driven pathways, dihydroceramide desaturase 1 was identified as an AR-regulated gene in mitotically active cells that promoted pro-metastatic phenotypes, and in advanced PCa proved to be highly associated with development of metastases, recurrence after therapeutic intervention and reduced overall survival. Taken together, these findings delineate AR function in mitotically active tumor cells, thus providing critical insight into the molecular basis by which AR promotes development of lethal PCa and nominate new avenues for therapeutic intervention.

Standardized ileal digestibility of amino acids in eight genotypes of barley fed to growing pigs.

To determine chemical composition, physical characteristics and standardized ileal digestibility (SID) of CP and amino acids (AA) in eight current hulled barley genotypes, an experiment with growing pigs has been conducted. These genotypes included Yool, Campanile, Lomerit, Travira, Anisette, Canberra, Metaxa and Fridericus. Growing barrows with an average initial BW of 30±2 kg were surgically fitted with simple T-cannulas at the distal ileum, and allotted to an 8×9 Youden square design with eight periods of 6 days each and nine pigs. Barley was the sole dietary source of CP and AA. On average, the eight genotypes contained on as-fed basis 10.7% CP, 15.2% total non-starch polysaccharides (NSP), 17.1% NDF and 4.1% ß-glucan, and had a mean test weight (TW) of 72.2 kg/hl. The SID of CP in the barley genotypes varied from 69% to 74%, and was greater (P<0.01) for genotypes Travira, Anisette and Metaxa compared to Yool and Campanile. Standardized ileal digestibility of Lys, Met and Trp (P<0.05) but not of Thr differed between genotypes. Moreover, barley genotypes differed in their standardized ileal digestible content (cSID) of CP and AA. Furthermore, SID and cSID of CP and most AA linearly decreased (P<0.05) with increasing NDF and total sugar content. Standardized ileal digestibility of CP and some AA and cSID of CP and most AA decreased linearly with increasing TW (P<0.05). Additionally, SID and cSID of CP and AA of most barley genotypes were lower when compared to tabulated values. In conclusion, a comprehensive database on chemical composition and SID of CP and AA in eight current barley genotypes has been made available. However, as present SID values are lower compared to feed tables, adjustments are required to minimize the risk of overestimating the actual protein value of barley for pigs.

Metabolic response to dietary fibre composition in horses.

The hypothesis for this study was that a higher dietary proportion of soluble fibre would result in stable and constant plasma metabolite and regulatory hormone concentrations. The study was a 4×4 Latin Square design with a sequence of 17 days adaptation to the ration followed by 8 sampling days. The feed rations consisted of only timothy hay (H), hay plus molassed sugar beet pulp combined with either whole oats (OB) or barley (BB) and hay plus a loose chaff-based concentrate (M). Four horses were fitted with permanent caecal cannulas and liquid caecal content was withdrawn manually and blood was drawn from the jugular vein at 0, 3 and 9 h postprandial. The horses were exercised daily at medium level for about 1 h. Samples were analysed for short-chain fatty acids (SCFA) and metabolic traits. Caecal SCFA and propionic acid concentrations increased with increased dietary starch and soluble fibre. The diet highest in soluble fibre (M) resulted in the highest plasma glucose and insulin concentrations in the morning, which then remained stable and constant throughout the day. A strong interaction (P<0.01) between time and diet was measured for plasma urea, glucose, insulin and leptin. The greatest variations in plasma glycaemic and insulinaemic responses were associated with the cereal grain diets (OB and BB). There were indications of a negative energy balance, which was reflected in a significantly higher plasma ß-hydroxybutyrate concentration and a numerically higher non-esterified fatty acid concentration. In conclusion, this study found that inclusion of soluble fibre resulted in increased total caecal SCFA and propionic acid concentrations. This consequently resulted in stable and constant plasma glycaemic and insulinaemic responses. Diets with a high content of soluble fibre provided enough energy for horses at medium work level.

Effect of xylanases on ileal viscosity, intestinal fiber modification, and apparent ileal fiber and nutrient digestibility of rye and wheat in growing pigs.

Two experiments were performed to study the effect of xylanase on ileal extract viscosity, in vivo fiber solubilization and degradation, and apparent ileal digestibility (AID) of fiber constituents, OM, CP, starch, and crude fat in rye and wheat in ileal-cannulated pigs. In Exp. 1, coarse rye without (NX) or with addition of xylanase from Aspergillus niger (AN), (BS), or (TR) was fed to 8 ileal-cannulated barrows (initial BW 30.9 ± 0.3 kg) for 1 wk each according to a double 4 × 4 Latin square design. In Exp. 2, fine rye, fine wheat, and coarse wheat with or without a combination of xylanase from and were fed to 6 ileal-cannulated barrows (initial BW 33.6 ± 0.5 kg) for 1 wk according to a 6 × 6 Latin square design with a 2 × 3 factorial arrangement of enzyme and cereal matrix. Chromic oxide (0.2%) was used as an inert marker. Ileal effluent was collected for 8 h on d 5 and 7 and pooled for analysis. In Exp. 1, TR reduced intestinal viscosity of pigs fed rye from 9.3 mPa·s in the control diet (NX) to 6.0 mPa·s ( < 0.001), whereas AN and BS had no effect. None of the enzymes changed the concentration of total arabinoxylan, high-molecular-weight arabinoxylan (HMW-AX), or arabinoxylan oligosaccharides (AXOS) in the liquid phase of digesta. In Exp. 2, the enzyme combination reduced intestinal viscosity for all 3 cereal matrices ( < 0.05), but the viscosity was much higher with fine rye (7.6 mPa·s) than with fine and coarse wheat (<1.7 mPa·s). Simultaneously, the total concentration of arabinoxylan in the liquid phase of digesta increased by 82.4% in fine wheat ( < 0.002) and by 45.9% in coarse wheat ( < 0.006), and AXOS increased 16-fold with enzyme addition. Similar effects of enzyme were not seen with rye. The concentration of xylooligosaccharides in the liquid phase of digesta increased with enzyme addition, but for xylose, it was only significant for wheat, for which it increased 3.9-fold ( < 0.001). None of the xylanases affected AID of arabinoxylan of rye in Exp. 1. In Exp. 2, the enzyme combination increased AID of arabinoxylan by 91% to 107% ( < 0.001) across cereal matrices. Enzyme addition did not affect AID of nutrients in any of the experiments except for a higher starch and crude fat digestibility of fine wheat with enzyme addition ( < 0.012) in Exp. 2. Collectively, the results suggest that xylanase is more efficient in degrading arabinoxylan from wheat than from rye.

Xylanase increased the ileal digestibility of nonstarch polysaccharides and concentration of low molecular weight nondigestible carbohydrates in pigs fed high levels of wheat distillers dried grains with solubles.

The objective was to study the effect of a commercially available xylanase (CAX), an experimental xylanase (EX), and EX in combination with protease (EXP) on the degradation of nondigestible carbohydrates (NDC) and apparent ileal digestibility (AID) of nutrients in wheat distillers dried grains with solubles (wDDGS). The control and 3 enzyme diets contained 96% wDDGS supplemented with vitamins, minerals, L-lysine, and chromic oxide as a digestibility marker in addition to enzyme premix. Eight ileal cannulated pigs were fed 4 experimental diets containing 96% wDDGS-a control diet or 1 of 3 diets with CAX, EX, or EXP-in a double 4 × 4 Latin square design. The experimental period lasted 7 d; adaptation lasted 4 d, and the ileal digesta were collected for 8 h on d 5 and 7, when spot samples of feces were also collected. Digesta samples were analyzed for NDC, total and soluble nonstarch polysaccharides (NSP), low molecular weight (LMW) NDC, OM, CP, fat, starch, and marker. Compared with the control diet, addition of CAX, EX, and EXP increased the AID of arabinoxylan by 32 (P < 0.001), 28 (P = 0.001), and 24% (P = 0.004), respectively. In addition, EXP increased the AID of noncellulosic polysaccharide glucose by 21% compared with the control (P = 0.005). Compared with the control, addition of EX, EXP, and CAX decreased the concentration of soluble arabinoxylan in ileal digesta by 40 (P < 0.0001), 40 (P < 0.0001), and 21% (P = 0.022), respectively. Furthermore, addition of CAX, EXP, and EX increased the concentration of LMW arabinoxylan in ileal digesta by 40 (P = 0.0001), 36 (P = 0.0006), and 24% (P = 0.023), respectively, compared with the control. Addition of EX and EXP decreased the concentration of soluble NSP of ileal digesta by 25 (P = 0.001) and 26% (P < 0.001), respectively, compared with the control diet. Addition of CAX (P < 0.0001) and EXP (P = 0.013) increased the arabinose-to-xylose ratio in the insoluble arabinoxylan fraction in ileal digesta compared with the control diet, and CAX increased the uronic acid-to-xylose ratio of the ileal insoluble NSP fraction (P < 0.0001) compared with the control diet. Enzyme addition did not affect AID of OM, CP, starch, and fat (P > 0.3). In conclusion, addition of xylanases to wDDGS diets increased the ileal digestibility of NSP and generated LMW NDC components in the small intestine of pigs but did not affect ileal digestibility of nutrients in the current study.

Fermentation and addition of enzymes to a diet based on high-moisture corn, rapeseed cake, and peas improve digestibility of nonstarch polysaccharides, crude protein, and phosphorus in pigs.

Fluctuating prices of cereals have led to an interest in alternative ingredients for feed. The aim of this study was to evaluate the effect of fermentation and the addition of nonstarch polysaccharide (NSP)-degrading enzymes on the ileal and total tract digestibility of nutrients of a diet based on locally grown crops. Four diets were fed including a nonfermented liquid standard grower diet (Control) and 3 experimental diets based on high-moisture corn, rapeseed cake, and peas fed as nonfermented liquid feed (nFLF), fermented liquid feed (FLF), or FLF supplemented with an enzyme mixture of ß-glucanase + xylanase + pectinase (FLF+Enz). The FLF was prepared by mixing feed and water (1:2.5, wt/wt) and, once daily, replacing 50% of the mixture with an equal amount of fresh feed and water. The diets were fed to 8 ileal cannulated barrows in a double Latin square design. Ileal digesta and feces were collected after an adaption period of 10 d. Results showed microbiologically good-quality fermented diets. The levels of Enterobacteriaceae were 5.1 to 5.4 log cfu/g in FLF and FLF+Enz vs. 6.3 log cfu/g in nFLF in the ileum and 5.1 to 5.2 log cfu/g in FLF and FLF+Enz vs. 6.3 log cfu/g in nFLF in the feces. Apparent total tract digestibility (ATTD) of CP was increased by fermentation (73.2% in FLF vs. 69.0% in nFLF; P = 0.033), and digestibility of P showed a tendency (P = 0.073) toward an increase. Addition of the enzyme mixture resulted in a pronounced reduction of dietary NSP compared with FLF (12.8% total NSP in FLF+Enz vs. 15.9% total NSP in FLF; P< 0.001), which also led to increased apparent ileal digestibility (AID) of total and insoluble NSP (total NSP, 31.1% in FLF+Enz vs. 13.6% in FLF; P = 0.002). The Control did not, in general, show higher digestibility values than the experimental diet. However, in the cases were it did, fermentation and enzyme addition brought the digestibility to the level of the Control. In conclusion, fermentation increased the ATTD of CP and the AID of P, with the same tendency (P ≤ 0.07) for the ATTD. Addition of NSP-degrading enzymes resulted in a pronounced reduction in the concentration of NSP in the feed along with increased AID of NSP. Hence, the experimental diet seems to be a possible alternative to a traditional diet for pigs.

Carbohydrate composition and in vitro digestibility of dry matter and nonstarch polysaccharides in corn, sorghum, and wheat and coproducts from these grains.

The objectives of this work were to determine carbohydrate composition and in vitro digestibility of DM and nonstarch polysaccharides (NSP) in corn, wheat, and sorghum and coproducts from these grains. In the initial part of this work, the carbohydrate composition of 12 feed ingredients was determined. The 12 ingredients included 3 grains (corn, sorghum, and wheat), 3 coproducts from the dry grind industry (corn distillers dried grains with solubles [DDGS] and 2 sources of sorghum DDGS), 4 coproducts from the wet milling industry (corn gluten meal, corn gluten feed, corn germ meal, and corn bran), and 2 coproducts from the flour milling industry (wheat middlings and wheat bran). Results indicated that grains contained more starch and less NSP compared with grain coproducts. The concentration of soluble NSP was low in all ingredients. Cellulose, arabinoxylans, and other hemicelluloses made up approximately 22, 49, and 29% (DM basis), respectively, of the NSP in corn and corn coproducts and approximately 25, 43, and 32% (DM basis), respectively, of the NSP in sorghum and sorghum DDGS. Cellulose, arabinoxylans, and other hemicelluloses made up approximately 16, 64, and 20% (DM basis), respectively, of the NSP in wheat and wheat coproducts. The concentration of lignin in grains was between 0.8 and 1.8% (DM basis), whereas coproducts contained between 2.2 and 11.5% lignin (DM basis). The in vitro ileal digestibility of NSP was close to zero or negative for all feed ingredients, indicating that pepsin and pancreas enzymes have no effect on in vitro degradation of NSP. A strong negative correlation ( = 0.97) between in vitro ileal digestibility of DM and the concentration of NSP in feed ingredients was observed. In vitro total tract digestibility of NSP ranged from 6.5% in corn bran to 57.3% in corn gluten meal. In conclusion, grains and grain coproducts contain mostly insoluble NSP and arabinoxylans make up the majority of the total NSP fraction. The in vitro digestibility of NSP depends on the amount and type of NSP and degree of lignification in the feed ingredient. The NSP composition of grains and grain coproducts plays an important role in determining the extent of fermentation of NSP; therefore, NSP composition influences the energy value of grains and grain coproducts.

Standardized ileal digestibility of amino acids in eight genotypes of soft winter wheat fed to growing pigs.

A study with growing pigs was conducted to determine the chemical composition and standardized ileal digestibility (SID) of CP and AA of 8 wheat genotypes that have recently been added to the German Descriptive Variety List. These genotypes included Tabasco, KWS Erasmus, Tobak, Skalmeje, Mulan, Event, Tommi, and Adler. The 8 genotypes were grown under identical environmental conditions on the same site, and they were harvested and processed under the same conditions. Nine barrows with an initial BW of 32 ± 2 kg were surgically fitted with simple ileal T-cannulas and allotted to a row-column design with 9 pigs and 8 periods of 6 d each. Wheat was the sole dietary source of CP and AA. Among the 8 wheat genotypes, contents of CP ranged from 10.9 to 13.3% (as-fed basis), whereas contents of total nonstarch polysaccharides ranged from 8.0 to 9.4% (as-fed basis). The SID of CP in the 8 genotypes ranged from 83 to 87%, with greatest ( = 0.01) values for Event and lowest ( = 0.01) for all other wheat genotypes. Intermediate SID of CP values were obtained for Adler and KWS Erasmus. For Lys, greater ( < 0.05) SID was observed in Adler (73%) and KWS Erasmus (74%) in comparison to Tommi, Tobak, and Mulan (69%). Adler had greater SID of Met (88%; = 0.01) when compared to Tabasco (86%); Tobak, Skalmeje, and Mulan (85%); and Tommi (84%). Among the 8 wheat genotypes, standardized ileal digestible content (cSID) of CP followed total CP content and ranged from 9.1 to 11.3% (as-fed basis). Standardized ileal digestible content of both CP and AA were greater ( < 0.001) in Adler compared to all other genotypes. For most AA, Tabasco had the lowest ( < 0.001; except for His, Trp, Asp, and Cys) cSID values of all wheat genotypes. The cSID of CP decreased ( < 0.001) as the starch content in the 8 wheat genotypes increased, but cSID of CP increased ( < 0.001) as the CP content in the 8 genotypes increased. Because SID and cSID of CP and most AA increased ( < 0.05) with lower test weight and falling number, these variables may aid to predict SID and cSID in wheat batches, whereas other nutrients such as fiber fractions are not suitable due to low variation among the 8 genotypes. The present study provides a comprehensive database on nutritional composition and SID of CP and AA of 8 wheat genotypes grown under identical conditions. Because the SID values in these genotypes are lower when compared to literature data, digestibility values in actual feed tables for wheat may overestimate their protein values and need to be updated.

Integrative molecular profiling of routine clinical prostate cancer specimens.

BACKGROUND: Comprehensive molecular profiling led to the recognition of multiple prostate cancer (PCa) molecular subtypes and driving alterations, but translating these findings to clinical practice is challenging. PATIENTS AND METHODS: We developed a formalin-fixed paraffin-embedded (FFPE) tissue compatible integrative assay for PCa molecular subtyping and interrogation of relevant genetic/transcriptomic alterations (MiPC). We applied MiPC, which combines capture-based next generation sequencing and quantitative reverse transcription PCR (qRT-PCR), to 53 FFPE PCa specimens representing cases not well represented in frozen tissue cohorts, including 8 paired primary tumor and lymph node metastases. Results were validated using multiplexed PCR based NGS and Sanger sequencing. RESULTS: We identified known and novel potential driving, somatic mutations and copy number alterations, including a novel BRAF T599_V600insHT mutation and CYP11B2 amplification in a patient treated with ketoconazole (a potent CYP11B2 inhibitor). qRT-PCR integration enabled comprehensive molecular subtyping and provided complementary information, such as androgen receptor (AR) target gene module assessment in advanced cases and SPINK1 over-expression. MiPC identified highly concordant profiles for all 8 tumor/lymph node metastasis pairs, consistent with limited heterogeneity amongst driving events. MiPC and exome sequencing were performed on separately isolated conventional acinar PCa and prostatic small cell carcinoma (SCC) components from the same FFPE resection specimen to enable direct comparison of histologically distinct components. While both components showed TMPRSS2:ERG fusions, the SCC component exclusively harbored complete TP53 inactivation (frameshift variant and copy loss) and two CREBBP mutations. CONCLUSIONS: Our results demonstrate the feasibility of integrative profiling of routine PCa specimens, which may have utility for understanding disease biology and enabling personalized medicine applications.

The effect of dietary carbohydrate composition on apparent total tract digestibility, feed mean retention time, nitrogen and water balance in horses.

A total of four diets with different carbohydrate composition were investigated in a 4×4 Latin square design experiment with four Norwegian Coldblooded trotter horses. The objective of the present study was to increase the fermentable fibre content and reduce the starch intake of the total ration obtained by partly substituting mature hay and barley with sugar beet pulp (SBP), a soluble fibre source. The diets investigated were hay only (HAY), hay (85% of dry matter intake (DMI)) and molassed SBP (15% of DMI) (SBP), hay (68% of DMI) and barley (32% of DMI) (BAR), and hay (68% of DMI), barley (26% of DMI) and SBP (6% of DMI) (BAR+SBP). The feeding level was 18.5, 17.3, 15.7 and 15.7 g DM/kg BW per day for the HAY, SBP, BAR and BAR+SBP diets, respectively. Each diet was fed for 18 days followed by 10 days of data collection, where apparent total tract digestibility (ATTD), total mean retention time (TMRT) of ytterbium-labelled hay, water balance, digestible energy (DE) intake and nitrogen balance were measured. An enzymatic chemical dietary fibre (DF) method was used to get detailed information on the composition and ATTD of the fibre fraction. Inclusion of SBP in the diet increased the ATTD of the constituent sugars galactose and arabinose (P<0.01). Feeding the HAY and SBP diets resulted in a lower TMRT owing to a higher DF intake than the BAR and BAR+SBP diets (P<0.01). There was no difference in water intake between HAY and SBP, but faecal dry matter was lower for HAY than the other diets (P=0.017), indicating that water was more tightly bound to fibre in the HAY diet. The diets were iso-energetic and provided enough DE and protein for light to moderate exercise for a 550 kg horse. In conclusion, this study showed that the DF intake had a larger effect on TMRT than partly substituting hay or barley with SBP, and that highly fermentable pectin-rich soluble DF from SBP maintains high nutrient utilization in horses.

Postprandial effects of test meals including concentrated arabinoxylan and whole grain rye in subjects with the metabolic syndrome: a randomised study.

BACKGROUND/OBJECTIVES: Prospective studies have shown an inverse relationship between whole grain consumption and the risk of type 2 diabetes, where short chain fatty acids (SCFA) may be involved. Our objective was to determine the effect of isolated arabinoxylan alone or in combination with whole grain rye kernels on postprandial glucose, insulin, free fatty acids (FFA), gut hormones, SCFA and appetite in subjects with the metabolic syndrome (MetS). SUBJECTS/METHODS: Fifteen subjects with MetS participated in this acute, randomised, cross-over study. The test meals each providing 50 g of digestible carbohydrate were as follows: semolina porridge added concentrated arabinoxylan (AX), rye kernels (RK) or concentrated arabinoxylan combined with rye kernels (AXRK) and semolina porridge as control (SE). A standard lunch was served 4 h after the test meals. Blood samples were drawn during a 6-h period, and appetite scores and breath hydrogen were assessed every 30 min. RESULTS: The AXRK meal reduced the acute glucose (P=0.005) and insulin responses (P<0.001) and the feeling of hunger (P=0.005; 0-360 min) compared with the control meal. The AX and AXRK meals increased butyrate and acetate concentrations after 6 h. No significant differences were found for the second meal responses of glucose, insulin, FFA, glucagon-like peptide-1 or ghrelin. CONCLUSIONS: Our results indicate a stimulatory effect of arabinoxylan on butyrate and acetate production, however, with no detectable effect on the second meal glucose response. It remains to be tested in a long-term study if a beneficial effect on the glucose response of the isolated arabinoxylan will be related to the SCFA production.

Effects of concentrated arabinoxylan and ß-glucan compared with refined wheat and whole grain rye on glucose and appetite in subjects with the metabolic syndrome: a randomized study.

BACKGROUND/OBJECTIVES: Several studies emphasise that arabinoxylan and ß-glucan have more beneficial effects on glucose metabolism than low-dietary fibre (DF) meals. Less attention has been paid to the effects of concentrated DF compared with whole grain. We compared the effects of DF and whole grain on glucose, hormone responses and appetite in subjects with the metabolic syndrome (MetS). SUBJECTS/METHODS: Fifteen subjects with MetS participated in this acute, randomised, cross-over intervention study. The test breads provided 50 g of digestible carbohydrate: wheat bread with concentrated arabinoxylan (AX) or ß-glucan (BG), rye bread with kernels (RK) and wheat bread (WB) as control. Blood samples were drawn for 270 min to determine glucose, insulin, glucagon-like peptide-1, glucose-dependent insulinotropic peptide (GIP) and ghrelin. Appetite score was addressed every 30 min. Ad libitum energy intake (EI) was measured 270 min after test meals. RESULTS: Compared with WB, BG and RK induced lower initial glycaemic responses (P<0.001), whereas AX only reduced the glucose peak value (P<0.001). RK reduced insulin (P<0.001) and GIP responses (P<0.001) compared with the other breads. BG lowered insulin responses more than AX (P<0.001). AX, BG and RK increased satiety feeling (P<0.001) more than WB, but did not differ significantly in terms of subsequent EI (P=0.089). CONCLUSION: BG and RK had beneficial impact on the glucose response, whereas AX had only effect on the postprandial glucose peak. The impact of the AX bread was influenced by higher protein content. Whether the metabolic effects of the breads are still present to mixed meals remains to be tested.

Targeting cell cycle and hormone receptor pathways in cancer.

The cyclin/cyclin-dependent kinase (CDK)/retinoblastoma (RB)-axis is a critical modulator of cell cycle entry and is aberrant in many human cancers. New nodes of therapeutic intervention are needed that can delay or combat the onset of malignancies. The antitumor properties and mechanistic functions of PD-0332991 (PD; a potent and selective CDK4/6 inhibitor) were investigated using human prostate cancer (PCa) models and primary tumors. PD significantly impaired the capacity of PCa cells to proliferate by promoting a robust G1-arrest. Accordingly, key regulators of the G1-S cell cycle transition were modulated including G1 cyclins D, E and A. Subsequent investigation demonstrated the ability of PD to function in the presence of existing hormone-based regimens and to cooperate with ionizing radiation to further suppress cellular growth. Importantly, it was determined that PD is a critical mediator of PD action. The anti-proliferative impact of CDK4/6 inhibition was revealed through reduced proliferation and delayed growth using PCa cell xenografts. Finally, first-in-field effects of PD on proliferation were observed in primary human prostatectomy tumor tissue explants. This study shows that selective CDK4/6 inhibition, using PD either as a single-agent or in combination, hinders key proliferative pathways necessary for disease progression and that RB status is a critical prognostic determinant for therapeutic efficacy. Combined, these pre-clinical findings identify selective targeting of CDK4/6 as a bona fide therapeutic target in both early stage and advanced PCa and underscore the benefit of personalized medicine to enhance treatment response.

Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome -- a randomized study (SYSDIET).

BACKGROUND: Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome. METHODS: We conducted a randomized dietary study lasting for 18-24 weeks in individuals with features of metabolic syndrome (mean age 55 years, BMI 31.6 kg m(-2) , 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids. RESULTS: Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (-0.18, mmol L(-1) 95% CI -0.35; -0.01, P = 0.04), LDL to HDL cholesterol (-0.15, -0.28; -0.00, P = 0.046) and apolipoprotein B to apolipoprotein A1 ratios (-0.04, -0.07; -0.00, P = 0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference -84, -133; -37 ng L(-1) , P = 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P = 0.049) and magnesium (mg, -0.23, -0.41; -0.05, P = 0.012) were associated with IL-1 Ra. CONCLUSIONS: Healthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation.

Evaluation of two external markers for measurement of ileal and total tract digestibility of pigs fed human-type diets.

External markers for determination of nutrient digestibility have often been evaluated in conventional dry feeds but less often in conventional feeds such as human-type diets used in animal model studies. In the present study, 5 ileal-cannulated pigs were fed 5 types of soft bread-based diets supplemented with Cr(2)O(3) and AIA as digestibility markers for 1 wk in a Latin square design. Ileal contents were collected twice for 5 h and a fecal grab sample was obtained once per week. Ileal and total tract digestibility of OM and nonstarch polysaccharides (NSP) based on the 2 markers were compared by linear regression. Across dietary treatments and site of collection, high correlation existed between digestibility values obtained with Cr(2)O(3) and AIA, resulting in a R(2) > 0.77 (P < 0.001) and a linear relation close to unity. For ileal samples, the correlation was poor, particularly for NSP, which had R(2) = 0.09 (P = 0.14) whereas OM had an R(2) = 0.52 (P <0.001). On the other hand, fecal grab samples led to R(2) > 0.92 (P < 0.001) for both OM and NSP. However, AIA gave higher values than Cr(2)O(3), particularly in samples with lower digestibility. The discrepancy is presumably caused by analytical difficulties due to a high fecal ash contents or interference with other components in the human-type diets.