121 research outputs found

    Spontaneous midgestation abortion associated with Bacteroides fragilis: a case report.

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    A midtrimester pregnancy loss, due to B. fragilis is described. We hypothesize that in early pregnancy anaerobic bacterial vaginosis has the greatest pathogenicity, while an intermediate (mixed) flora is most dangerous in midtrimester miscarriages, and that aerobic vaginitis is more dangerous than anaerobes towards the second half of the pregnancy. Unfortunately, no screen and treat policy has yet been proven to be sufficiently powerful to prevent the vast majority of infection-related prematurity. © 2005 Taylor & Francis.status: publishe

    Efficient reverse-engineering of a developmental gene regulatory network

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    This is the final version of the article. Available from the publisher via the DOI in this record.Understanding the complex regulatory networks underlying development and evolution of multi-cellular organisms is a major problem in biology. Computational models can be used as tools to extract the regulatory structure and dynamics of such networks from gene expression data. This approach is called reverse engineering. It has been successfully applied to many gene networks in various biological systems. However, to reconstitute the structure and non-linear dynamics of a developmental gene network in its spatial context remains a considerable challenge. Here, we address this challenge using a case study: the gap gene network involved in segment determination during early development of Drosophila melanogaster. A major problem for reverse-engineering pattern-forming networks is the significant amount of time and effort required to acquire and quantify spatial gene expression data. We have developed a simplified data processing pipeline that considerably increases the throughput of the method, but results in data of reduced accuracy compared to those previously used for gap gene network inference. We demonstrate that we can infer the correct network structure using our reduced data set, and investigate minimal data requirements for successful reverse engineering. Our results show that timing and position of expression domain boundaries are the crucial features for determining regulatory network structure from data, while it is less important to precisely measure expression levels. Based on this, we define minimal data requirements for gap gene network inference. Our results demonstrate the feasibility of reverse-engineering with much reduced experimental effort. This enables more widespread use of the method in different developmental contexts and organisms. Such systematic application of data-driven models to real-world networks has enormous potential. Only the quantitative investigation of a large number of developmental gene regulatory networks will allow us to discover whether there are rules or regularities governing development and evolution of complex multi-cellular organisms.Funding: The laboratory of Johannes Jaeger and this study in particular was funded by the MEC-EMBL agreement for the EMBL/CRG Research Unit in Systems Biology, by Grant 153 (MOPDEV) of the ERANet: ComplexityNET program, by SGR Grant 406 from the Catalan funding agency AGAUR, by grant BFU2009-10184 from the Spanish Ministry of Science, and by European Commission grant FP7-KBBE-2011-5/289434 (BioPreDyn). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    Evolutionary connectionism: algorithmic principles underlying the evolution of biological organisation in evo-devo, evo-eco and evolutionary transitions

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    The mechanisms of variation, selection and inheritance, on which evolution by natural selection depends, are not fixed over evolutionary time. Current evolutionary biology is increasingly focussed on understanding how the evolution of developmental organisations modifies the distribution of phenotypic variation, the evolution of ecological relationships modifies the selective environment, and the evolution of reproductive relationships modifies the heritability of the evolutionary unit. The major transitions in evolution, in particular, involve radical changes in developmental, ecological and reproductive organisations that instantiate variation, selection and inheritance at a higher level of biological organisation. However, current evolutionary theory is poorly equipped to describe how these organisations change over evolutionary time and especially how that results in adaptive complexes at successive scales of organisation (the key problem is that evolution is self-referential, i.e. the products of evolution change the parameters of the evolutionary process). Here we first reinterpret the central open questions in these domains from a perspective that emphasises the common underlying themes. We then synthesise the findings from a developing body of work that is building a new theoretical approach to these questions by converting well-understood theory and results from models of cognitive learning. Specifically, connectionist models of memory and learning demonstrate how simple incremental mechanisms, adjusting the relationships between individually-simple components, can produce organisations that exhibit complex system-level behaviours and improve the adaptive capabilities of the system. We use the term “evolutionary connectionism” to recognise that, by functionally equivalent processes, natural selection acting on the relationships within and between evolutionary entities can result in organisations that produce complex system-level behaviours in evolutionary systems and modify the adaptive capabilities of natural selection over time. We review the evidence supporting the functional equivalences between the domains of learning and of evolution, and discuss the potential for this to resolve conceptual problems in our understanding of the evolution of developmental, ecological and reproductive organisations and, in particular, the major evolutionary transitions

    Can computational efficiency alone drive the evolution of modularity in neural networks?

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    Some biologists have abandoned the idea that computational efficiency in processing multipart tasks or input sets alone drives the evolution of modularity in biological networks. A recent study confirmed that small modular (neural) networks are relatively computationally-inefficient but large modular networks are slightly more efficient than non-modular ones. The present study determines whether these efficiency advantages with network size can drive the evolution of modularity in networks whose connective architecture can evolve. The answer is no, but the reason why is interesting. All simulations (run in a wide variety of parameter states) involving gradualistic connective evolution end in non-modular local attractors. Thus while a high performance modular attractor exists, such regions cannot be reached by gradualistic evolution. Non-gradualistic evolutionary simulations in which multi-modularity is obtained through duplication of existing architecture appear viable. Fundamentally, this study indicates that computational efficiency alone does not drive the evolution of modularity, even in large biological networks, but it may still be a viable mechanism when networks evolve by non-gradualistic means

    Refining transcriptional regulatory networks using network evolutionary models and gene histories

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    <p>Abstract</p> <p>Background</p> <p>Computational inference of transcriptional regulatory networks remains a challenging problem, in part due to the lack of strong network models. In this paper we present evolutionary approaches to improve the inference of regulatory networks for a family of organisms by developing an evolutionary model for these networks and taking advantage of established phylogenetic relationships among these organisms. In previous work, we used a simple evolutionary model and provided extensive simulation results showing that phylogenetic information, combined with such a model, could be used to gain significant improvements on the performance of current inference algorithms.</p> <p>Results</p> <p>In this paper, we extend the evolutionary model so as to take into account gene duplications and losses, which are viewed as major drivers in the evolution of regulatory networks. We show how to adapt our evolutionary approach to this new model and provide detailed simulation results, which show significant improvement on the reference network inference algorithms. Different evolutionary histories for gene duplications and losses are studied, showing that our adapted approach is feasible under a broad range of conditions. We also provide results on biological data (<it>cis</it>-regulatory modules for 12 species of <it>Drosophila</it>), confirming our simulation results.</p

    Intergenomic Rearrangements after Polyploidization of Kengyilia thoroldiana (Poaceae: Triticeae) Affected by Environmental Factors

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    Polyploidization is a major evolutionary process. Approximately 70–75% species of Triticeae (Poaceae) are polyploids, involving 23 genomes. To investigate intergenomic rearrangements after polyploidization of Triticeae species and to determine the effects of environmental factors on them, nine populations of a typical polyploid Triticeae species, Kengyilia thoroldiana (Keng) J.L.Yang et al. (2n = 6x = 42, StStPPYY), collected from different environments, were studied using genome in situ hybridization (GISH). We found that intergenomic rearrangements occurred between the relatively large P genome and the small genomes, St (8.15%) and Y (22.22%), in polyploid species via various types of translocations compared to their diploid progenitors. However, no translocation was found between the relatively small St and Y chromosomes. Environmental factors may affect rearrangements among the three genomes. Chromosome translocations were significantly more frequent in populations from cold alpine and grassland environments than in populations from valley and lake-basin habitats (P<0.05). The relationship between types of chromosome translocations and altitude was significant (r = 0.809, P<0.01). Intergenomic rearrangements associated with environmental factors and genetic differentiation of a single basic genome should be considered as equally important genetic processes during species' ecotype evolution

    Identifying potential survival strategies of HIV-1 through virus-host protein interaction networks

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    Background: The National Institute of Allergy and Infectious Diseases has launched the HIV-1 Human Protein Interaction Database in an effort to catalogue all published interactions between HIV-1 and human proteins. In order to systematically investigate these interactions functionally and dynamically, we have constructed an HIV-1 human protein interaction network. This network was analyzed for important proteins and processes that are specific for the HIV life-cycle. In order to expose viral strategies, network motif analysis was carried out showing reoccurring patterns in virus-host dynamics.Results: Our analyses show that human proteins interacting with HIV form a densely connected and central sub-network within the total human protein interaction network. The evaluation of this sub-network for connectivity and centrality resulted in a set of proteins essential for the HIV life-cycle. Remarkably, we were able to associate proteins involved in RNA polymerase II transcription with hubs and proteasome formation with bottlenecks. Inferred network motifs show significant over-representation of positive and negative feedback patterns between virus and host. Strikingly, such patterns have never been reported in combined virus-host systems.Conclusions: HIV infection results in a reprioritization of cellular processes reflected by an increase in the relative importance of transcriptional machinery and proteasome formation. We conclude that during the evolution of HIV, some patterns of interaction have been selected for resulting in a system where virus proteins preferably interact with central human proteins for direct control and with proteasomal proteins for indirect control over the cellular processes. Finally, the patterns described by network motifs illustrate how virus and host interact with one another
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