Effects of flaxseed encapsulation on biohydrogenation of polyunsaturated fatty acids by ruminal microorganisms: feedlot performance, carcass quality, and tissue fatty acid composition

Citation: Alvarado-Gilis, C. A., Aperce, C. C., Miller, K. A., Van Bibber-Krueger, C. L., Klamfoth, D., & Drouillard, J. S. (2015). Effects of flaxseed encapsulation on biohydrogenation of polyunsaturated fatty acids by ruminal microorganisms: feedlot performance, carcass quality, and tissue fatty acid composition. Journal of Animal Science, 93(9), 4368-4376. doi:10.2527/jas2015-9171The objective of this study was to evaluate the efficacy of protecting PUFA within ground flaxseed against ruminal biohydrogenation by encapsulating them in a matrix consisting of a 1:1 blend of ground flaxseed and dolomitic lime hydrate (L-Flaxseed). Crossbreed heifers (n = 462, 346 +/- 19 kg) were blocked by weight and randomly assigned to pens. Pens were assigned to 1 of 6 dietary treatments in a randomized complete block design. Treatment 1 consisted of a combination of 54.6% steam-flaked corn (SFC), 30.0% wet corn gluten feed, 8.0% roughage, and supplement (0% flaxseed). In treatments 2 and 3, a proportion of SFC was replaced with 3 and 6% flaxseed, respectively; in treatments 4, 5, and 6, SFC was replaced with 2, 4, or 6% L-Flaxseed, respectively. Cattle were fed for 140 or 168 d and then harvested in a commercial abattoir where carcass data were collected. Approximately 24 h after harvest, carcasses were evaluated for 12th-rib fat thickness, KPH, LM area, marbling score, and USDA yield and quality grades. Samples of LM were also obtained for determination of long-chain fatty acid profiles. Cattle that were fed diets with 4 and 6% L-Flaxseed consumed less feed than other treatments (P 0.05). Supplementation with flaxseed increased (P 99%; increases for Flaxseed and L-Flaxseed of 0.095 and 0.140 mg of ALA/g of tissue for each percentage of flaxseed added). This study indicates that a matrix consisting of dolomitic lime hydrate is an effective barrier to ruminal biohydrogenation of PUFA; however, adverse effects on DMI limit the amounts that can be fed

Effects of crystalline menthol on blood metabolites in Holstein steers and in vitro volatile fatty acid and gas production

Citation: Van Bibber-Krueger, C. L., Miller, K. A., Aperce, C. C., Alvarado-Gilis, C. A., Higgins, J. J., & Drouillard, J. S. (2016). Effects of crystalline menthol on blood metabolites in Holstein steers and in vitro volatile fatty acid and gas production. Journal of Animal Science, 94(3), 1170-1178. doi:10.2527/jas2015-8779Fifty-two Holstein steers (573 +/- 9.92 kg BW) were used to determine if oral administration of crystalline menthol would induce changes in endogenous secretions of IGF-1 and circulating concentrations of glucose, lactate, and plasma urea nitrogen (PUN). Steers were blocked by BW and assigned within block to treatment. Treatments consisted of 0, 0.003, 0.03, or 0.3% crystalline menthol (DM basis) added to the diet. Animals were housed in individual, partially covered pens equipped with feed bunks and automatic water fountains. On d 1 of the experiment, blood samples were obtained via jugular venipuncture at 0, 6, 12, 18, and 24 h after feeding. Treatment administration commenced on d 2, and blood samples were again drawn at 0, 6, 12, 18, and 24 h after feeding. This blood-sampling schedule was repeated on d 9, 16, 23, and 30. Plasma was analyzed for PUN, glucose, and lactate concentrations. Serum was used to analyze IGF-1 concentration. Body weights were measured on d 1, 9, 16, 23, and 30. To accompany the live animal phase, in vitro fermentations were performed using ruminal fluid cultures. Measurements included VFA concentrations and fermentative gas production for cultures containing crystalline menthol at 0, 0.003, 0.03, or 0.3% of substrate DM. Addition of menthol to the diet of steers resulted in a treatment x day interaction (P 0.21). In conclusion, menthol supplementation minimally affected blood parameters associated with growth or ruminal fermentative activity

Potentials of Mean Force for Protein Structure Prediction Vindicated, Formalized and Generalized

Understanding protein structure is of crucial importance in science, medicine and biotechnology. For about two decades, knowledge based potentials based on pairwise distances -- so-called "potentials of mean force" (PMFs) -- have been center stage in the prediction and design of protein structure and the simulation of protein folding. However, the validity, scope and limitations of these potentials are still vigorously debated and disputed, and the optimal choice of the reference state -- a necessary component of these potentials -- is an unsolved problem. PMFs are loosely justified by analogy to the reversible work theorem in statistical physics, or by a statistical argument based on a likelihood function. Both justifications are insightful but leave many questions unanswered. Here, we show for the first time that PMFs can be seen as approximations to quantities that do have a rigorous probabilistic justification: they naturally arise when probability distributions over different features of proteins need to be combined. We call these quantities reference ratio distributions deriving from the application of the reference ratio method. This new view is not only of theoretical relevance, but leads to many insights that are of direct practical use: the reference state is uniquely defined and does not require external physical insights; the approach can be generalized beyond pairwise distances to arbitrary features of protein structure; and it becomes clear for which purposes the use of these quantities is justified. We illustrate these insights with two applications, involving the radius of gyration and hydrogen bonding. In the latter case, we also show how the reference ratio method can be iteratively applied to sculpt an energy funnel. Our results considerably increase the understanding and scope of energy functions derived from known biomolecular structures

Knowledge-based energy functions for computational studies of proteins

This chapter discusses theoretical framework and methods for developing knowledge-based potential functions essential for protein structure prediction, protein-protein interaction, and protein sequence design. We discuss in some details about the Miyazawa-Jernigan contact statistical potential, distance-dependent statistical potentials, as well as geometric statistical potentials. We also describe a geometric model for developing both linear and non-linear potential functions by optimization. Applications of knowledge-based potential functions in protein-decoy discrimination, in protein-protein interactions, and in protein design are then described. Several issues of knowledge-based potential functions are finally discussed.Comment: 57 pages, 6 figures. To be published in a book by Springe

Cardiovascular End Points and Mortality Are Not Closer Associated With Central Than Peripheral Pulsatile Blood Pressure Components

Pulsatile blood pressure (BP) confers cardiovascular risk. Whether associations of cardiovascular end points are tighter for central systolic BP (cSBP) than peripheral systolic BP (pSBP) or central pulse pressure (cPP) than peripheral pulse pressure (pPP) is uncertain. Among 5608 participants (54.1% women; mean age, 54.2 years) enrolled in nine studies, median follow-up was 4.1 years. cSBP and cPP, estimated tonometrically from the radial waveform, averaged 123.7 and 42.5 mm Hg, and pSBP and pPP 134.1 and 53.9 mm Hg. The primary composite cardiovascular end point occurred in 255 participants (4.5%). Across fourths of the cPP distribution, rates increased exponentially (4.1, 5.0, 7.3, and 22.0 per 1000 person-years) with comparable estimates for cSBP, pSBP, and pPP. The multivariable-adjusted hazard ratios, expressing the risk per 1-SD increment in BP, were 1.50 (95% CI, 1.33–1.70) for cSBP, 1.36 (95% CI, 1.19–1.54) for cPP, 1.49 (95% CI, 1.33–1.67) for pSBP, and 1.34 (95% CI, 1.19–1.51) for pPP (P\u3c0.001). Further adjustment of cSBP and cPP, respectively, for pSBP and pPP, and vice versa, removed the significance of all hazard ratios. Adding cSBP, cPP, pSBP, pPP to a base model including covariables increased the model fit (P\u3c0.001) with generalized R2 increments ranging from 0.37% to 0.74% but adding a second BP to a model including already one did not. Analyses of the secondary end points, including total mortality (204 deaths), coronary end points (109) and strokes (89), and various sensitivity analyses produced consistent results. In conclusion, associations of the primary and secondary end points with SBP and pulse pressure were not stronger if BP was measured centrally compared with peripherally

The International Database of Central Arterial Properties for Risk Stratification: Research Objectives and Baseline Characteristics of Participants

OBJECTIVE To address to what extent central hemodynamic measurements, improve risk stratification, and determine outcome-based diagnostic thresholds, we constructed the International Database of Central Arterial Properties for Risk Stratification (IDCARS), allowing a participant-level meta-analysis. The purpose of this article was to describe the characteristics of IDCARS participants and to highlight research perspectives. METHODS Longitudinal or cross-sectional cohort studies with central blood pressure measured with the SphygmoCor devices and software were included. RESULTS The database included 10,930 subjects (54.8% women; median age 46.0 years) from 13 studies in Europe, Africa, Asia, and South America. The prevalence of office hypertension was 4,446 (40.1%), of which 2,713 (61.0%) were treated, and of diabetes mellitus was 629 (5.8%). The peripheral and central systolic/diastolic blood pressure averaged 129.5/78.7 mm Hg and 118.2/79.7 mm Hg, respectively. Mean aortic pulse wave velocity was 7.3 m per seconds. Among 6,871 participants enrolled in 9 longitudinal studies, the median follow-up was 4.2 years (5th–95th percentile interval, 1.3–12.2 years). During 38,957 person-years of follow-up, 339 participants experienced a composite cardiovascular event and 212 died, 67 of cardiovascular disease. CONCLUSIONS IDCARS will provide a unique opportunity to investigate hypotheses on central hemodynamic measurements that could not reliably be studied in individual studies. The results of these analyses might inform guidelines and be of help to clinicians involved in the management of patients with suspected or established hypertension

PoPMuSiC 2.1: a web server for the estimation of protein stability changes upon mutation and sequence optimality

ABSTRACT:Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Inferring stabilizing mutations from protein phylogenies : application to influenza hemagglutinin

One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (ΔΔG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a further test, we use our phylogenetic inference approach to predict stabilizing mutations to influenza hemagglutinin. We introduce these mutations into a temperature-sensitive influenza virus with a defect in its hemagglutinin gene and experimentally demonstrate that some of the mutations allow the virus to grow at higher temperatures. Our work therefore describes a powerful new approach for predicting stabilizing mutations that can be successfully applied even to large, complex proteins such as hemagglutinin. This approach also makes a mathematical link between phylogenetics and experimentally measurable protein properties, potentially paving the way for more accurate analyses of molecular evolution

Early prevention of diabetes microvascular complications in people with hyperglycaemia in Europe. ePREDICE randomized trial. Study protocol, recruitment and selected baseline data

Objectives To assess the effects of early management of hyperglycaemia with antidiabetic drugs plus lifestyle intervention compared with lifestyle alone, on microvascular function in adults with pre-diabetes. Methods Trial design: International, multicenter, randomised, partially double-blind, placebo-controlled, clinical trial. Participants Males and females aged 45-74 years with IFG, IGT or IFG+IGT, recruited from primary care centres in Australia, Austria, Bulgaria, Greece, Kuwait, Poland, Serbia, Spain and Turkey. Intervention Participants were randomized to placebo; metformin 1.700 mg/day; linagliptin 5 mg/day or fixed-dose combination of linagliptin/metformin. All patients were enrolled in a lifestyle intervention program (diet and physical activity). Drug intervention will last 2 years. Primary Outcome: Composite end-point of diabetic retinopathy estimated by the Early Treatment Diabetic Retinopathy Study Score, urinary albumin to creatinine ratio, and skin conductance in feet estimated by the sudomotor index. Secondary outcomes in a subsample include insulin sensitivity, beta-cell function, biomarkers of inflammation and fatty liver disease, quality of life, cognitive function, depressive symptoms and endothelial function. Results One thousand three hundred ninety one individuals with hyperglycaemia were assessed for eligibility, 424 excluded after screening, 967 allocated to placebo, metformin, linagliptin or to fixed-dose combination of metformin + linagliptin. A total of 809 people (91.1%) accepted and initiated the assigned treatment. Study sample after randomization was well balanced among the four groups. No statistical differences for the main risk factors analysed were observed between those accepting or rejecting treatment initiation. At baseline prevalence of diabetic retinopathy was 4.2%, severe neuropathy 5.3% and nephropathy 5.7%. Conclusions ePREDICE is the first -randomized clinical trial with the aim to assess effects of different interventions (lifestyle and pharmacological) on microvascular function in people with prediabetes. The trial will provide novel data on lifestyle modification combined with glucose lowering drugs for the prevention of early microvascular complications and diabetes

Cardiovascular end points and mortality are not closer associated with central than peripheral pulsatile blood pressure components

none32Pulsatile blood pressure (BP) confers cardiovascular risk. Whether associations of cardiovascular end points are tighter for central systolic BP (cSBP) than peripheral systolic BP (pSBP) or central pulse pressure (cPP) than peripheral pulse pressure (pPP) is uncertain. Among 5608 participants (54.1% women; mean age, 54.2 years) enrolled in nine studies, median follow-up was 4.1 years. cSBP and cPP, estimated tonometrically from the radial waveform, averaged 123.7 and 42.5 mm Hg, and pSBP and pPP 134.1 and 53.9 mm Hg. The primary composite cardiovascular end point occurred in 255 participants (4.5%). Across fourths of the cPP distribution, rates increased exponentially (4.1, 5.0, 7.3, and 22.0 per 1000 person-years) with comparable estimates for cSBP, pSBP, and pPP. The multivariable-adjusted hazard ratios, expressing the risk per 1-SD increment in BP, were 1.50 (95% CI, 1.33-1.70) for cSBP, 1.36 (95% CI, 1.19-1.54) for cPP, 1.49 (95% CI, 1.33-1.67) for pSBP, and 1.34 (95% CI, 1.19-1.51) for pPP (P<0.001). Further adjustment of cSBP and cPP, respectively, for pSBP and pPP, and vice versa, removed the significance of all hazard ratios. Adding cSBP, cPP, pSBP, pPP to a base model including covariables increased the model fit (P<0.001) with generalized R2 increments ranging from 0.37% to 0.74% but adding a second BP to a model including already one did not. Analyses of the secondary end points, including total mortality (204 deaths), coronary end points (109) and strokes (89), and various sensitivity analyses produced consistent results. In conclusion, associations of the primary and secondary end points with SBP and pulse pressure were not stronger if BP was measured centrally compared with peripherally.noneHuang, Qi-Fang; Aparicio, Lucas S; Thijs, Lutgarde; Wei, Fang-Fei; Melgarejo, Jesus D; Cheng, Yi-Bang; Sheng, Chang-Sheng; Yang, Wen-Yi; Gilis-Malinowska, Natasza; Boggia, José; Niiranen, Teemu J; Wojciechowska, Wiktoria; Stolarz-Skrzypek, Katarzyna; Barochiner, Jessica; Ackermann, Daniel; Tikhonoff, Valérie; Ponte, Belen; Pruijm, Menno; Casiglia, Edoardo; Narkiewicz, Krzysztof; Filipovský, Jan; Czarnecka, Danuta; Kawecka-Jaszcz, Kalina; Jula, Antti M; Bochud, Murielle; Vanassche, Thomas; Verhamme, Peter; Struijker-Boudier, Harry A J; Wang, Ji-Guang; Zhang, Zhen-Yu; Li, Yan; Staessen, Jan AHuang, Qi-Fang; Aparicio, Lucas S; Thijs, Lutgarde; Wei, Fang-Fei; Melgarejo, Jesus D; Cheng, Yi-Bang; Sheng, Chang-Sheng; Yang, Wen-Yi; Gilis-Malinowska, Natasza; Boggia, José; Niiranen, Teemu J; Wojciechowska, Wiktoria; Stolarz-Skrzypek, Katarzyna; Barochiner, Jessica; Ackermann, Daniel; Tikhonoff, Valérie; Ponte, Belen; Pruijm, Menno; Casiglia, Edoardo; Narkiewicz, Krzysztof; Filipovský, Jan; Czarnecka, Danuta; Kawecka-Jaszcz, Kalina; Jula, Antti M; Bochud, Murielle; Vanassche, Thomas; Verhamme, Peter; Struijker-Boudier, Harry A J; Wang, Ji-Guang; Zhang, Zhen-Yu; Li, Yan; Staessen, Jan