31 research outputs found
A robust class of stable proteins in the 2D HPC model
Abstract. The inverse protein folding problem is that of designing an amino acid sequence which has a prescribed native protein fold. This problem arises in drug design where a particular structure is necessary to ensure proper protein-protein interactions. The input to the inverse protein folding problem is a shape and the goal is to design a protein sequence with a unique native fold that closely approximates the input shape. Gupta et al. [1] introduced a design in the 2D HP model of Dill that can be used to approximate any given (2D) shape. They conjectured that the protein sequences of their design are stable but only proved the stability for an infinite class of very basic structures. In [2], we have introduced a refinement of the HP model, in which the cysteine and noncysteine hydrophobic monomers are distinguished and SS-bridges which two cysteines can form are taken into account in the energy function. This model was called the 2D HPC model. In [2], the snake structures in the HPC model were introduced and it was conjectured that they are stable. In this paper, we show that this conjecture is true for a subclass of snake structures. This subclass is robust enough to approximate any given 2D shape, although more coarsely than the general constructible structures proposed i
Studies on equine milk and comparative studies on equine and bovine milk systems
The composition of equine milk differs considerably from that of the milk of the principal dairying species, i.e., the cow, buffalo, goat and sheep. Because equine milk resembles human milk in many respects and is claimed to have special therapeutic properties, it is becoming increasingly popular in Western Europe, where it is produced on large farms in several countries. Equine milk is considered to be highly digestible, rich in essential nutrients and to possess an optimum whey protein:casein ratio, making it very suitable as a substitute for bovine milk in paediatric dietetics. There is some scientific basis for the special nutritional and health-giving properties of equine milk but this study provides a comprehensive analysis of the composition and physico-chemical properties of equine milk which is required to fully exploit its potential in human nutrition. Quantification and distribution of the nitrogenous components and principal salts of equine milk are reported. The effects of the high concentration of ionic calcium, large casein micelles (~ 260 nm), low protein, lack of a sulphydryl group in equine β-lactoglobulin and a very low level of κ-casein on the physico-chemical properties of equine milk are reported. This thesis provides an insight into the stability of equine casein micelles to heat, ethanol, high pressure, rennet or acid. Differences in rennet- and acid-induced coagulation between equine and bovine milk are attributed not only to the low casein content of equine milk but also to differences in the mechanism by which the respective micelles are stabilized. It has been reported that β-casein plays a role in the stabilization of equine casein micelles and proteomic techniques support this view. In this study, equine κ-casein appeared to be resistant to hydrolysis by calf chymosin but equine β-casein was readily hydrolysed. Resolution of equine milk proteins by urea-PAGE showed the multi-phosphorylated isoforms of equine αs- and β-caseins and capillary zone electrophoresis showed 3 to 7 phosphorylated residues in equine β-casein. In vitro digestion of equine β-casein by pepsin and Corolase PP™ did not produce casomorphins BCM-5 or BCM-7, believed to be harmful to human health. Electron microscopy provided very clear, detailed images of equine casein micelles in their native state and when renneted or acidified. Equine milk formed flocs rather then a gel when renneted or acidified which is supported by dynamic oscillatory analysis. The results presented in this thesis will assist in the development of new products from equine milk for human consumption which will retain some of its unique compositional and health-giving properties
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Investigating novel prebiotic blends and their impact on markers of satiety
The purpose of this project was to develop a novel blend of prebiotics with the potential to influence perceptions of satiety and thus food intake. Prebiotics beneficially modulate the composition of the gut microbiota, they are fermented primarily in the ceacum resulting in the production of metabolites, including acetate and propionate. These metabolites are thought to impact appetite regulation by acting as a ligand, with a high affinity to G-coupled receptors (GPR42/3) located on L-cells, throughout the length of the colon. A subsequent stimulation of circulating satiety hormones triggers anorexogenic pathways involved in reducing food intake and increasing satiety. It is therefore hypothesised that using blends of prebiotics to increase SCFA production along the length of the colon might be of benefit in weight management.
Initially a literature review is presented, evaluating dietary intervention studies that have explored the satiety inducing effects of different prebiotics/prebiotic candidates on various human populations. In the reviewed 17/27 intervention studies prebiotics were associated with increased satiety. Variations in study design, dose and study food matrix might explain the disparity in the results.
The work of screening eleven commonly consumed prebiotics/prebiotic candidates for their fermentation characteristics is described in the first experimental chapter. Using an in vitro batch culture model of the gut (n=3), those prebiotics that stimulated the growth of acetate and propionate producing bacterial species, such as Bifidobacterium and Propionibacterium specifically at later fermentation time points (24-48h) (indicating a slower fermentation), were considered for further study. Inulin was identified as the most bifidogenic of all the substrates.
Three substrates that performed well in the first experimental section were blended with inulin to produce 3 novel prebiotic blends (inulin + resistant starch, inulin + α-gluco-oligosaccharides, and inulin + arabinoxylan). The fermentation characteristics of these blends were assessed in depth using a 3-stage continuous culture colonic model (n=3). The focus was on the influence of these prebiotic blends on the third fermentation vessel, which simulates the distal region of the colon. The hypothesis that residual prebiotic activity in this vessel might be associated with a flatter and more sustained SCFA spike following consumption, and that this might lead to better appetite control. Of the 3 blends, I+RS and I+ABX outperformed
I+GLOS exhibiting a sustained fermentation towards V3, however I+ABX was the frontrunner, due to the levels of propionate produced, including those in V3, which was desirable.
In a 9-week crossover, placebo controlled and double blinded human appetite study. I+ABX was consumed daily by healthy weight men. The primary endpoint was satiety and ad libitum energy intake on a study visit day. Secondary endpoints were prebiotic effects assessed in stool and urine. Subjective satiety scores were not influenced however there was a statistically significant reduction in energy intake during the ad libitum lunch of 34.28Kcal. If extended over three meals this might equate to a <100 Kcal reduction in energy intake per day, more than sufficient to elicit progressive weight loss or to contribute to weight maintenance. The intervention also induced significant increases in the abundance of Bifidobacterium (P=0.017) and Propionibacterium (P=0.021) in stool samples and an increase in the concentration of acetate. This research has demonstrated a pipeline for the development of prebiotics with the potential for use in weight management products.
Chronic consumption of LC-FOS with ABX significantly reduced food intake and therefore supplementation of the diet with I+ABX may be a useful tool in weight management. Further work is needed to understand the mechanism and to establish additional prebiotic benefits associated with consuming this blend. Our blended product is being patented by our industrial sponsor and may be explored in further clinical intervention study over extended time frames with weight control as the endpoint
Making sense of mixtures : chromatographic separations of plant, insect and microbial biomolecules.
Thesis (Ph.D.)-University of Natal, Pietermaritzburg, 1996.No abstract available