Search results for "Simulation"
showing 10 items of 5095 documents
Genetic variability at neutral markers, quantitative trait loci and trait in a subdivided population under selection
2003
Abstract Genetic variability in a subdivided population under stabilizing and diversifying selection was investigated at three levels: neutral markers, QTL coding for a trait, and the trait itself. A quantitative model with additive effects was used to link genotypes to phenotypes. No physical linkage was introduced. Using an analytical approach, we compared the diversity within deme (HS) and the differentiation (FST) at the QTL with the genetic variance within deme (VW) and the differentiation (QST) for the trait. The difference between FST and QST was shown to depend on the relative amounts of covariance between QTL within and between demes. Simulations were used to study the effect of se…
The Origins of Lactase Persistence in Europe
2009
Lactase persistence (LP) is common among people of European ancestry, but with the exception of some African, Middle Eastern and southern Asian groups, is rare or absent elsewhere in the world. Lactase gene haplotype conservation around a polymorphism strongly associated with LP in Europeans (−13,910 C/T) indicates that the derived allele is recent in origin and has been subject to strong positive selection. Furthermore, ancient DNA work has shown that the −13,910*T (derived) allele was very rare or absent in early Neolithic central Europeans. It is unlikely that LP would provide a selective advantage without a supply of fresh milk, and this has lead to a gene-culture coevolutionary model w…
Network dynamics of eukaryotic LTR retroelements beyond phylogenetic trees
2009
Abstract Background Sequencing projects have allowed diverse retroviruses and LTR retrotransposons from different eukaryotic organisms to be characterized. It is known that retroviruses and other retro-transcribing viruses evolve from LTR retrotransposons and that this whole system clusters into five families: Ty3/Gypsy, Retroviridae, Ty1/Copia, Bel/Pao and Caulimoviridae. Phylogenetic analyses usually show that these split into multiple distinct lineages but what is yet to be understood is how deep evolution occurred in this system. Results We combined phylogenetic and graph analyses to investigate the history of LTR retroelements both as a tree and as a network. We used 268 non-redundant …
Distributed and Lumped Parameter Models for the Characterization of High Throughput Bioreactors
2016
Next generation bioreactors are being developed to generate multiple human cell-based tissue analogs within the same fluidic system, to better recapitulate the complexity and interconnection of human physiology. The effective development of these devices requires a solid understanding of their interconnected fluidics, to predict the transport of nutrients and waste through the constructs and improve the design accordingly. In this work, we focus on a specific model of bioreactor, with multiple input/outputs, aimed at gen- erating osteochondral constructs, i.e., a biphasic construct in which one side is cartilagi- nous in nature, while the other is osseous. We next develop a general computat…
CO rebinding kinetics and molecular dynamics simulations highlight dynamic regulation of internal cavities in human cytoglobin
2013
Abstract: Cytoglobin (Cygb) was recently discovered in the human genome and localized in different tissues. It was suggested to play tissue-specific protective roles, spanning from scavenging of reactive oxygen species in neurons to supplying oxygen to enzymes in fibroblasts. To shed light on the functioning of such versatile machinery, we have studied the processes supporting transport of gaseous heme ligands in Cygb. Carbon monoxide rebinding shows a complex kinetic pattern with several distinct reaction intermediates, reflecting rebinding from temporary docking sites, second order recombination, and formation (and dissociation) of a bis-histidyl heme hexacoordinated reaction intermediate…
Improvement of ALT decay kinetics by all-oral HCV treatment: Role of NS5A inhibitors and differences with IFN-based regimens
2017
Background Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR. Study design Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR. Kinetic-models and Cox-analysis were used to assess determinants of ALT-decay and normalization. Results HCV-RNA kinetics was biphasic, reflecting …
Structural analyses of a hypothetical minimal metabolism
2007
By integrating data from comparative genomics and large-scale deletion studies, we previously proposed a minimal gene set comprising 206 protein-coding genes. To evaluate the consistency of the metabolism encoded by such a minimal genome, we have carried out a series of computational analyses. Firstly, the topology of the minimal metabolism was compared with that of the reconstructed networks from natural bacterial genomes. Secondly, the robustness of the metabolic network was evaluated by simulated mutagenesis and, finally, the stoichiometric consistency was assessed by automatically deriving the steady-state solutions from the reaction set. The results indicated that the proposed minimal …
Distortion of symmetrical introgression in a hybrid zone: evidence for locus-specific selection and uni-directional range expansion
2006
The fate of species integrity upon natural hybridization depends on the interaction between selection and dispersal. The relative significance of these processes may be studied in the initial phase of contact before selection and gene flow reach equilibrium. Here we study a hybrid zone of two salamander species, Lyciasalamandra antalyana and Lyciasalamandra billae, at the initial phase of hybridization. We quantify the degree and mode of introgression using nuclear and mtDNA markers. The hybrid zone can be characterized as an abrupt transition zone, the central hybrid zone being only c. 400 m, but introgressed genes were traced up to 3 km. Introgression was traced in both sexes but gene flo…
Metabolic Networks of Sodalis glossinidius: A Systems Biology Approach to Reductive Evolution
2012
BackgroundGenome reduction is a common evolutionary process affecting bacterial lineages that establish symbiotic or pathogenic associations with eukaryotic hosts. Such associations yield highly reduced genomes with greatly streamlined metabolic abilities shaped by the type of ecological association with the host. Sodalis glossinidius, the secondary endosymbiont of tsetse flies, represents one of the few complete genomes available of a bacterium at the initial stages of this process. In the present study, genome reduction is studied from a systems biology perspective through the reconstruction and functional analysis of genome-scale metabolic networks of S. glossinidius.ResultsThe functiona…
Estimation of Purkinje trees from electro-anatomical mapping of the left ventricle using minimal cost geodesics
2015
The electrical activation of the heart is a complex physiological process that is essential for the understanding of several cardiac dysfunctions, such as ventricular tachycardia (VT). Nowadays, patient-specific activation times on ventricular chambers can be estimated from electro-anatomical maps, providing crucial information to clinicians for guiding cardiac radio-frequency ablation treatment. However, some relevant electrical pathways such as those of the Purkinje system are very difficult to interpret from these maps due to sparsity of data and the limited spatial resolution of the system. We present here a novel method to estimate these fast electrical pathways from the local activati…