n-Heptane hydroconversion over nickel-loaded aluminum- and/or boron-containing BEA zeolites prepared by recrystallization of magadiite varieties

Phase-pure [Al]BEA and [Al,B]BEA zeolites, prepared by solid-state recrystallization of synthetic aluminum-containing magadiites and conventionally synthesized [B]BEA, were tested, after ion exchange with nickel, as bifunctional catalysts for hydroconversion of n-heptane. The reducibility of nickel ions incorporated into BEA zeolites by ion exchange was investigated by temperature-programmed reduction (TPR). The acidity of the samples was characterized with strong (pyridine (Py), ammonia (NH3)) and weak (nitrogen) bases. The adsorbed bases were studied by transmission FT-IR (Py), diffuse reflectance infrared Fourier-transform (DRIFT) spectroscopy (N2), and temperature-programmed ammonia evolution (TPAE, NH3). Over Ni/H-[B]BEA the reactants were completely converted via fast hydrogenolysis, whereas this reaction pathway plays only a negligible role in the hydroconversion over Ni/H-[Al]BEA and Ni/H-[Al,B]BEA zeolites. Boron-containing BEA zeolites were less active catalysts than the boron-free catalyst in the principal unimolecular hydroconversion reactions. However, incorporation of boron into the framework of BEA zeolite results in a considerable selectivity shift towards isomerization. Results suggest that the acid strength of bridged hydroxyls, probed with weak (N2) and strong basis (pyridine), was found to be similar in the boron-free and boron-containing BEA samples. The decrease in the isomerization rate and the increase of the apparent activation energy upon incorporation of boron may be attributed to the decrease in the heat of n-heptane adsorption

A reappraisal of the impact of dairy foods and milk fat on cardiovascular disease risk

Background This review provides a reappraisal of the potential effects of dairy foods, including dairy fats, on cardiovascular disease (CVD)/coronary heart disease (CHD) risk. Commodities and foods containing saturated fats are of particular focus as current public dietary recommendations are directed toward reducing the intake of saturated fats as a means to improve the overall health of the population. A conference of scientists from different perspectives of dietary fat and health was convened in order to consider the scientific basis for these recommendations. Aims This review and summary of the conference focus on four key areas related to the biology of dairy foods and fats and their potential impact on human health: (a) the effect of dairy foods on CVD in prospective cohort studies; (b) the impact of dairy fat on plasma lipid risk factors for CVD; (c) the effects of dairy fat on non-lipid risk factors for CVD; and (d) the role of dairy products as essential contributors of micronutrients in reference food patterns for the elderly. Conclusions Despite the contribution of dairy products to the saturated fatty acid composition of the diet, and given the diversity of dairy foods of widely differing composition, there is no clear evidence that dairy food consumption is consistently associated with a higher risk of CVD. Thus, recommendations to reduce dairy food consumption irrespective of the nature of the dairy product should be made with cautionJ. Bruce German, Robert A. Gibson, Ronald M. Krauss, Paul Nestel, Benoît Lamarche, Wija A. van Staveren, Jan M. Steijns, Lisette C. P. G. M. de Groot, Adam L. Lock and Frédéric Destaillat

Protein type, protein dose, and age modulate dietary protein digestion and phenylalanine absorption kinetics and plasma phenylalanine availability in humans

This is the final version. Available from the publisher via the DOI in this record.BACKGROUND: Dietary protein ingestion stimulates muscle protein synthesis by providing amino acids to the muscle. The magnitude and duration of the postprandial increase in muscle protein synthesis rates are largely determined by dietary protein digestion and amino acid absorption kinetics. OBJECTIVE: We assessed the impact of protein type, protein dose, and age on dietary protein digestion and amino acid absorption kinetics in vivo in humans. METHODS: We included data from 18 randomized controlled trials with a total of 602 participants [age: 53 ± 23 y; BMI (kg/m2): 24.8 ± 3.3] who consumed various quantities of intrinsically l-[1-13C]-phenylalanine-labeled whey (n = 137), casein (n = 393), or milk (n = 72) protein and received intravenous infusions of l-[ring-2H5]-phenylalanine, which allowed us to assess protein digestion and phenylalanine absorption kinetics and the postprandial release of dietary protein-derived phenylalanine into the circulation. The effect of aging on these processes was assessed in a subset of 82 young (aged 22 ± 3 y) and 83 older (aged 71 ± 5 y) individuals. RESULTS: A total of 50% ± 14% of dietary protein-derived phenylalanine appeared in the circulation over a 5-h postprandial period. Casein ingestion resulted in a smaller (45% ± 11%), whey protein ingestion in an intermediate (57% ± 10%), and milk protein ingestion in a greater (65% ± 13%) fraction of dietary protein-derived phenylalanine appearing in the circulation (P < 0.001). The postprandial availability of dietary protein-derived phenylalanine in the circulation increased with the ingestion of greater protein doses (P < 0.05). Protein digestion and phenylalanine absorption kinetics were attenuated in older when compared with young individuals, with 45% ± 10% vs. 51% ± 14% of dietary protein-derived phenylalanine appearing in the circulation, respectively (P = 0.001). CONCLUSIONS: Protein type, protein dose, and age modulate dietary protein digestion and amino acid absorption kinetics and subsequent postprandial plasma amino acid availability in vivo in humans. These trials were registered at clinicaltrials.gov as NCT00557388, NCT00936039, NCT00991523, NCT01317511, NCT01473576, NCT01576848, NCT01578590, NCT01615276, NCT01680146, NCT01820975, NCT01986842, and NCT02596542, and at http://www.trialregister.nl as NTR3638, NTR3885, NTR4060, NTR4429, and NTR4492

BMP7 increases protein synthesis in SW1353 cells and determines rRNA levels in a NKX3-2-dependent manner

BMP7 is a morphogen capable of counteracting the OA chondrocyte hypertrophic phenotype via NKX3-2. NKX3-2 represses expression of RUNX2, an important transcription factor for chondrocyte hypertrophy. Since RUNX2 has previously been described as an inhibitor for 47S pre-rRNA transcription, we hypothesized that BMP7 positively influences 47S pre-rRNA transcription through NKX3-2, resulting in increased protein translational capacity. Therefor SW1353 cells and human primary chondrocytes were exposed to BMP7 and rRNA (18S, 5.8S, 28S) expression was determined by RT-qPCR. NKX3-2 knockdown was achieved via transfection of a NKX3-2-specific siRNA duplex. Translational capacity was assessed by the SUNsET assay, and 47S pre-rRNA transcription was determined by transfection of a 47S gene promoter-reporter plasmid. BMP7 treatment increased protein translational capacity. This was associated by increased 18S and 5.8S rRNA and NKX3-2 mRNA expression, as well as increased 47S gene promotor activity. Knockdown of NKX3-2 led to increased expression of RUNX2, accompanied by decreased 47S gene promotor activity and rRNA expression, an effect BMP7 was unable to restore. Our data demonstrate that BMP7 positively influences protein translation capacity of SW1353 cells and chondrocytes. This is likely caused by an NKX3-2-dependent activation of 47S gene promotor activity. This finding connects morphogen-mediated changes in cellular differentiation to an aspect of ribosome biogenesis via key transcription factors central to determining the chondrocyte phenotype

BMP7 increases protein synthesis in SW1353 cells and determines rRNA levels in a NKX3-2-dependent manner

BMP7 is a morphogen capable of counteracting the OA chondrocyte hypertrophic phenotype via NKX3-2. NKX3-2 represses expression of RUNX2, an important transcription factor for chondrocyte hypertrophy. Since RUNX2 has previously been described as an inhibitor for 47S pre-rRNA transcription, we hypothesized that BMP7 positively influences 47S pre-rRNA transcription through NKX3-2, resulting in increased protein translational capacity. Therefor SW1353 cells and human primary chondrocytes were exposed to BMP7 and rRNA (18S, 5.8S, 28S) expression was determined by RT-qPCR. NKX3-2 knockdown was achieved via transfection of a NKX3-2-specific siRNA duplex. Translational capacity was assessed by the SUNsET assay, and 47S pre-rRNA transcription was determined by transfection of a 47S gene promoter-reporter plasmid. BMP7 treatment increased protein translational capacity. This was associated by increased 18S and 5.8S rRNA and NKX3-2 mRNA expression, as well as increased 47S gene promotor activity. Knockdown of NKX3-2 led to increased expression of RUNX2, accompanied by decreased 47S gene promotor activity and rRNA expression, an effect BMP7 was unable to restore. Our data demonstrate that BMP7 positively influences protein translation capacity of SW1353 cells and chondrocytes. This is likely caused by an NKX3-2-dependent activation of 47S gene promotor activity. This finding connects morphogen-mediated changes in cellular differentiation to an aspect of ribosome biogenesis via key transcription factors central to determining the chondrocyte phenotype

Development of a cyclic-inverso AHSG/Fetuin A-based peptide for inhibition of calcification in osteoarthritis

OBJECTIVE: Ectopic calcification is an important contributor to chronic diseases, such as osteoarthritis. Currently, no effective therapies exist to counteract calcification. We developed peptides derived from the calcium binding domain of human Alpha-2-HS-Glycoprotein (AHSG/Fetuin A) to counteract calcification. METHODS: A library of seven 30 amino acid (AA) long peptides, spanning the 118 AA Cystatin 1 domain of AHSG, were synthesized and evaluated in an in vitro calcium phosphate precipitation assay. The best performing peptide was modified (cyclic, retro-inverso and combinations thereof) and evaluated in cellular calcification models and the rat MCLT + MMT osteoarthritis model. RESULTS: A cyclic peptide spanning AA 1-30 of mature AHSG showed clear inhibition of calcium phosphate precipitation in the nM-pM range that far exceeded the biological activity of the linear peptide variant or bovine Fetuin. Biochemical and electron microscopy analyses of calcium phosphate particles revealed a similar, but distinct, mode of action in comparison with bFetuin. A cyclic-inverso variant of the AHSG 1-30 peptide inhibited calcification of human articular chondrocytes, vascular smooth muscle cells and during osteogenic differentiation of bone marrow derived stromal cells. Lastly, we evaluated the effect of intra-articular injection of the cyclic-inverso AHSG 1-30 peptide in a rat osteoarthritis model. A significant improvement was found in histopathological osteoarthritis score and animal mobility. Serum levels of IFNγ were found to be lower in AHSG 1-30 peptide treated animals. CONCLUSIONS: The cyclic-inverso AHSG 1-30 peptide directly inhibits the calcification process and holds the potential for future application in osteoarthritis