12 research outputs found

    Neighborhoods of trees in circular orderings

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    In phylogenetics, a common strategy used to construct an evolutionary tree for a set of species X is to search in the space of all such trees for one that optimizes some given score function (such as the minimum evolution, parsimony or likelihood score). As this can be computationally intensive, it was recently proposed to restrict such searches to the set of all those trees that are compatible with some circular ordering of the set X. To inform the design of efficient algorithms to perform such searches, it is therefore of interest to find bounds for the number of trees compatible with a fixed ordering in the neighborhood of a tree that is determined by certain tree operations commonly used to search for trees: the nearest neighbor interchange (nni), the subtree prune and regraft (spr) and the tree bisection and reconnection (tbr) operations. We show that the size of such a neighborhood of a binary tree associated with the nni operation is independent of the tree’s topology, but that this is not the case for the spr and tbr operations. We also give tight upper and lower bounds for the size of the neighborhood of a binary tree for the spr and tbr operations and characterize those trees for which these bounds are attained

    Heterarchy of Transcription Factors Driving Basal and Luminal Cell Phenotypes in Human Urothelium

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    Cell differentiation is effected by complex networks of transcription factors that co-ordinate re-organisation of the chromatin landscape. The hierarchies of these relationships can be difficult to dissect. During in vitro differentiation of normal human uro-epithelial cells, formaldehyde-assisted isolation of regulatory elements (FAIRE-seq) and RNA-seq were used to identify alterations in chromatin accessibility and gene expression changes following activation of the nuclear receptor PPARG as a differentiation-initiating event. Regions of chromatin identified by FAIRE-seq as having altered accessibility during differentiation were found to be enriched with sequence-specific binding motifs for transcription factors predicted to be involved in driving basal and differentiated urothelial cell phenotypes, including FOXA1, P63, GRHL2, CTCF and GATA3. In addition, co-occurrence of GATA3 motifs was observed within sub-sets of differentiation-specific peaks containing P63 or FOXA1 after induction of differentiation. Changes in abundance of GRHL2, GATA3, and P63 were observed in immunoblots of chromatin-enriched extracts. Transient siRNA knockdown of P63 revealed that P63 favoured a basal-like phenotype by inhibiting differentiation and promoting expression of basal marker genes. GATA3 siRNA prevented differentiation-associated downregulation of P63 protein and transcript, and demonstrated positive feedback of GATA3 on PPARG transcript, but showed no effect on FOXA1 transcript or protein expression. This approach indicates that as a transcriptionally-regulated programme, urothelial differentiation operates as a heterarchy wherein GATA3 is able to co-operate with FOXA1 to drive expression of luminal marker genes, but that P63 has potential to transrepress expression of the same genes

    Visionary management in the diagnostic and prognostic innovation model

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    The ability to perceive the world emergently is of particular importance. The vision of the ideal system considered as the analysis method, is widely used. Its indisputable advantage is that it does not require significant investments to carry out the analysis of a current situation, but nevertheless it is undoubtedly a difficult method demanding the high ability of predictive thinking

    A single community dominates structure and function of a mixture of multiple methanogenic communities

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    The ecology of microbes frequently involves the mixing of entire communities (community coalescence), for example, flooding events, host excretion, and soil tillage [ 1, 2 ], yet the consequences of this process for community structure and function are poorly understood [ 3–7 ]. Recent theory suggests that a community, due to coevolution between constituent species, may act as a partially cohesive unit [ 8–11 ], resulting in one community dominating after community coalescence. This dominant community is predicted to be the one that uses resources most efficiently when grown in isolation [ 11 ]. We experimentally tested these predictions using methanogenic communities, for which efficient resource use, quantified by methane production, requires coevolved cross-feeding interactions between species [ 12 ]. After propagation in laboratory-scale anaerobic digesters, community composition (determined from 16S rRNA sequencing) and methane production of mixtures of communities closely resembled that of the single most productive community grown in isolation. Analysis of each community’s contribution toward the final mixture suggests that certain combinations of taxa within a community might be co-selected as a result of coevolved interactions. As a corollary of these findings, we also show that methane production increased with the number of inoculated communities. These findings are relevant to the understanding of the ecological dynamics of natural microbial communities, as well as demonstrating a simple method of predictably enhancing microbial community function in biotechnology, health, and agriculture [ 13 ]

    Predicting the structure and function of coalesced microbial communities: Most efficient community dominates community mix

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    Immigration has major impacts on both the structure and function of communities and evolutionary dynamics of populations. While most work on immigration deals with relatively low numbers and diversity of immigrants, this does not capture microbial community dynamics, which frequently involve the coalescence of entire communities. The general consequences, if any, of such community coalescence are unclear, although existing theoretical and empirical studies suggest coalescence can result in single communities dominating resulting communities. A recent extension8 of classical ecological theory may provide a simple explanation: communities that exploit niches more fully and efficiently prevent species from other communities invading. Here, we test this prediction using complex anaerobic microbial communities, for which methane production provides a measure of resource use efficiency at community scale. We found that communities producing the most methane when grown in isolation dominated in mixtures of communities. As a consequence, the total methane production increased with the number of communities used as an inoculum. In addition to providing a practical method for enhancing biogas production during anaerobic digestion, these results are likely to be relevant to many other microbial communities. As such, it may be possible to predictably manipulate microbial community function for other biotechnological processes, health and agriculture

    Genome sequences identify three families of Coleoptera as morphologically derived click beetles (Elateridae)

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    Plastoceridae Crowson, 1972, Drilidae Blanchard, 1845 and Omalisidae Lacordaire, 1857 (Elateroidea) are families of the Coleoptera with obscure phylogenetic relationships and modified morphology showing neotenic traits such as soft bodies, reduced wing cases and larviform females. We shotgun sequenced genomes of Plastocerus, Drilus and Omalisus and incorporated them into data matrices of 66 and 4202 single-copy nuclear genes representing Elateroidea. Phylogenetic analyses indicate their terminal positions within the broadly defined well-sclerotized and fully metamorphosed Elateridae and thus Omalisidae should now be considered as Omalisinae stat. nov. in Elateridae Leach, 1815. The results support multiple independent origins of incomplete metamorphosis in Elateridae and indicate the parallel evolution of morphological and ecological traits. Unlike other neotenic elateroids derived from the supposedly pre-adapted aposematically coloured and unpalatable soft-bodied elateroids, such as fireflies (Lampyridae) and net-winged beetles (Lycidae), omalisids and drilids evolved from well-sclerotized click beetles. These findings suggest sudden morphological shifts through incomplete metamorphosis, with important implications for macroevolution, including reduced speciation rate and high extinction risk in unstable habitats. Precise phylogenetic placement is necessary for studies of the molecular mechanisms of ontogenetic shifts leading to profoundly changed morphology
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