Novel Changes in Discoidal High Density Lipoprotein Morphology: A Molecular Dynamics Study

AbstractApoA-I is a uniquely flexible lipid-scavenging protein capable of incorporating phospholipids into stable particles. Here we report molecular dynamics simulations on a series of progressively smaller discoidal high density lipoprotein particles produced by incremental removal of palmitoyloleoylphosphatidylcholine via four different pathways. The starting model contained 160 palmitoyloleoylphosphatidylcholines and a belt of two antiparallel amphipathic helical lipid-associating domains of apolipoprotein (apo) A-I. The results are particularly compelling. After a few nanoseconds of molecular dynamics simulation, independent of the starting particle and method of size reduction, all simulated double belts of the four lipidated apoA-I particles have helical domains that impressively approximate the x-ray crystal structure of lipid-free apoA-I, particularly between residues 88 and 186. These results provide atomic resolution models for two of the particles produced by in vitro reconstitution of nascent high density lipoprotein particles. These particles, measuring 95Å and 78Å by nondenaturing gradient gel electrophoresis, correspond in composition and in size/shape (by negative stain electron microscopy) to the simulated particles with molar ratios of 100:2 and 50:2, respectively. The lipids of the 100:2 particle family form minimal surfaces at their monolayer-monolayer interface, whereas the 50:2 particle family displays a lipid pocket capable of binding a dynamic range of phospholipid molecules

Operon prediction in Pyrococcus furiosus

Identification of operons in the hyperthermophilic archaeon Pyrococcus furiosus represents an important step to understanding the regulatory mechanisms that enable the organism to adapt and thrive in extreme environments. We have predicted operons in P.furiosus by combining the results from three existing algorithms using a neural network (NN). These algorithms use intergenic distances, phylogenetic profiles, functional categories and gene-order conservation in their operon prediction. Our method takes as inputs the confidence scores of the three programs, and outputs a prediction of whether adjacent genes on the same strand belong to the same operon. In addition, we have applied Gene Ontology (GO) and KEGG pathway information to improve the accuracy of our algorithm. The parameters of this NN predictor are trained on a subset of all experimentally verified operon gene pairs of Bacillus subtilis. It subsequently achieved 86.5% prediction accuracy when applied to a subset of gene pairs for Escherichia coli, which is substantially better than any of the three prediction programs. Using this new algorithm, we predicted 470 operons in the P.furiosus genome. Of these, 349 were validated using DNA microarray data

Recent progress on univariate and multivariate polynomial and spline quasi-interpolants

Polynomial and spline quasi-interpolants (QIs) are practical and effective approximation operators. Among their remarkable properties, let us cite for example: good shape properties, easy computation and evaluation (no linear system to solve), uniform boundedness independently of the degree (polynomials) or of the partition (splines), good approximation order. We shall emphasize new results on various types of univariate and multivariate polynomial or spline QIs, depending on the nature of coefficient functionals, which can be differential, discrete or integral. We shall also present some applications of QIs to numerical methods

Selection for growth rate and body size have altered the expression profiles of somatotropic axis genes in chickens.

The growth hormone / insulin-like growth factor-1 (GH/IGF-1) pathway of the somatotropic axis is the major controller for growth rate and body size in vertebrates, but the effect of selection on the expression of GH/IGF-1 somatotropic axis genes and their association with body size and growth performance in farm animals is not fully understood. We analyzed a time series of expression profiles of GH/IGF-1 somatotropic axis genes in two chicken breeds, the Daweishan mini chickens and Wuding chickens, and the commercial Avian broilers hybrid exhibiting markedly different body sizes and growth rates. We found that growth rate and feed conversion efficiency in Daweishan mini chickens were significantly lower than those in Wuding chickens and Avian broilers. The Wuding and Daweishan mini chickens showed higher levels of plasma GH, pituitary GH mRNA but lower levels of hepatic growth hormone receptor (GHR) mRNA than in Avian broilers. Daweishan mini chickens showed significantly lower levels of plasma IGF-1, thigh muscle and hepatic IGF-1 mRNA than did Avian broilers and Wuding chickens. These results suggest that the GH part of the somatotropic axis is the main regulator of growth rate, while IGF-1 may regulate both growth rate and body weight. Selection for growth performance and body size have altered the expression profiles of somatotropic axis genes in a breed-, age-, and tissue-specific manner, and manner, and alteration of regulatory mechanisms of these genes might play an important role in the developmental characteristics of chickens

Comparison of plasma hormone concentrations.

<p>Plasma concentration of growth hormone (GH) (a), growth hormone binding protein (GHBP) (b), insulin-like growth factor-1 (IGF-1) (c) and insulin-like growth factor-1 binding protein 2 (IGFBP2) (d) of the Daweishan mini chicken and Wuding chicken breeds, and the commercial Avian broiler hybrid at weeks 0, 4, 8 and 12. Statistical significance of difference among chickens at a specific age is indicated by asterisks (*: P<0.05; **: P<0.01). Statistical significance among different ages within a breed / hybrid is indicated with letters (lower case: P<0.05; capitals: P<0.01).</p

Comparison of growth hormone receptor (GHR) mRNA expression.

<p>GHR mRNA abundance in the liver (a), breast muscles (b) and in thigh muscles (c) from the Daweishan mini chicken and the Wuding chicken breeds, and the commercial Avian broiler hybrid at weeks 0, 4, 8 and 12. Statistical significance of difference among chickens at a specific age is indicated by asterisks (*: P<0.05; **: P<0.01). Statistical significance among different ages within a breed / hybrid is indicated with letters (lower case: P<0.05; capitals: P<0.01).</p