Graph Transformations and Game Theory: A Generative Mechanism for Network Formation

Many systems can be described in terms of networks with characteristic structural properties. To better understand the formation and the dynamics of complex networks one can develop generative models. We propose here a generative model (named dynamic spatial game) that combines graph transformations and game theory. The idea is that a complex network is obtained by a sequence of node-based transformations determined by the interactions of nodes present in the network. We model the node-based transformations by using graph grammars and the interactions between the nodes by using game theory. We illustrate dynamic spatial games on a couple of examples: the role of cooperation in tissue formation and tumor development and the emergence of patterns during the formation of ecological networks

The role of breast-feeding in infant immune system: a systems perspective on the intestinal microbiome

BACKGROUND: The human intestinal microbiota changes from being sparsely populated and variable to possessing a mature, adult-like stable microbiome during the first 2 years of life. This assembly process of the microbiota can lead to either negative or positive effects on health, depending on the colonization sequence and diet. An integrative study on the diet, the microbiota, and genomic activity at the transcriptomic level may give an insight into the role of diet in shaping the human/microbiome relationship. This study aims at better understanding the effects of microbial community and feeding mode (breast-fed and formula-fed) on the immune system, by comparing intestinal metagenomic and transcriptomic data from breast-fed and formula-fed babies.RESULTS: We re-analyzed a published metagenomics and host gene expression dataset from a systems biology perspective. Our results show that breast-fed samples co-express genes associated with immunological, metabolic, and biosynthetic activities. The diversity of the microbiota is higher in formula-fed than breast-fed infants, potentially reflecting the weaker dependence of infants on maternal microbiome. We mapped the microbial composition and the expression patterns for host systems and studied their relationship from a systems biology perspective, focusing on the differences.CONCLUSIONS: Our findings revealed that there is co-expression of more genes in breast-fed samples but lower microbial diversity compared to formula-fed. Applying network-based systems biology approach via enrichment of microbial species with host genes revealed the novel key relationships of the microbiota with immune and metabolic activity. This was supported statistically by data and literature

Cryptic successors unrevealed even by network analysis: A comparative study of two paper wasp species

Understanding queen succession could be a key contribution to the better understanding of the origins and evolution of eusociality. In order to investigate the nature of organizational changes during queen succession, we analyzed two closely related paper wasp species (Ropalidia cyathiformis and Ropalidia marginata). We compared the effects of in vivo and in silico queen removal on the structure of their interaction networks (the former resulting in queenless colonies with potential queens). We studied several structural measures. There is no major structural difference between full (queenright) and in silico queen-removed colonies but there are major differences between queenless and in silico queen-removed ones. This suggests that queen succession is accompanied by a major reorganization of the society, in Rm but not so much in Rc. We also analysed the centrality ranks of potential queens and found that their positional importance changes a lot during queen succession in R. marginata, as they are processed in the colony. In the queenright colonies of R. marginata, the direction of links is a better predictor of the identity of the potential queen than the strength of links

Strong asymmetrical inter-specific relationships in food web simulations

In complex ecosystem models, relationships between species include a large number of direct interactions and indirect effects. In order to unveil some simple and better understandable relationships, it is useful to study the asymmetry of inter-specific effects. We present a simple approach for this based on stochastic food web simulations from previous studies. We refer to the Prince William Sound (Gulf of Alaska) marine ecosystem model for illustration. Real data were used to parameterize a dynamical food web model. Through simulations and sensitivity analysis, we determined the strength of the effects between all species. We calculated the asymmetry between the mutual effects species have on each other, and selected the top 5% most asymmetrical interactions. The set of these highly asymmetrical relationships is illustrated by a separate graph in which we calculated the positional importance of the species and correlated this to other independent properties such as population size and trophic position. Results suggest that halibut is the key species dominating this system of asymmetrical interactions, but sablefish and adult arrowtooth flounder also seem to be of high importance. Nearshore demersals display the highest number of connections in the graph of asymmetrical links, suggesting that this trophic group regulates the dynamics of many species in the food web. This approach identifies key interactions and most asymmetrical relationships, potentially increasing the efficiency of management efforts and aiding conservation efforts

Analyzing various models of Circadian Clock and Cell Cycle coupling

The daily rhythm can influence the proliferation rate of many cell types. In the mammalian system the transcription of the cell cycle regulatory protein Wee1 is controlled by the circadian clock. Zamborszky et al. (2007) present a computational model coupling the cell cycle and circadian rhythm, showing that this coupling can lead to multimodal cell cycle time distributions. Biological data points to additional couplings, including a link back from the cell cycle to the circadian clock. Proper modelling of this coupling requires a more detailed description of both parts of the model. Hence, we aim at further extending and analysing earlier models using a combination of modelling techniques and computer software, including CoSBI lab, BIOCHAM, and GINsim

Protein Kinase C α Is a Central Signaling Node and Therapeutic Target for Breast Cancer Stem Cells

The epithelial-mesenchymal transition program becomes activated during malignant progression and can enrich for cancer stem cells (CSCs). We report that inhibition of protein kinase C α (PKCα) specifically targets CSCs but has little effect on non-CSCs. The formation of CSCs from non-stem cells involves a shift from EGFR to PDGFR signaling and results in the PKCα-dependent activation of FRA1. We identified an AP-1 molecular switch in which c-FOS and FRA1 are preferentially utilized in non-CSCs and CSCs, respectively. PKCα and FRA1 expression is associated with the aggressive triple-negative breast cancers, and the depletion of FRA1 results in a mesenchymal-epithelial transition. Hence, identifying molecular features that shift between cell states can be exploited to target signaling components critical to CSCs.National Cancer Institute (U.S.) (Grant P01-CA080111)National Institutes of Health (U.S.) (Grant R01-CA078461

The 2009 multiwavelength campaign on Mrk 421: Variability and correlation studies

We performed a 4.5-month multi-instrument campaign (from radio to VHE gamma rays) on Mrk421 between January 2009 and June 2009, which included VLBA, F-GAMMA, GASP-WEBT, Swift, RXTE, Fermi-LAT, MAGIC, and Whipple, among other instruments and collaborations. Mrk421 was found in its typical (non-flaring) activity state, with a VHE flux of about half that of the Crab Nebula, yet the light curves show significant variability at all wavelengths, the highest variability being in the X-rays. We determined the power spectral densities (PSD) at most wavelengths and found that all PSDs can be described by power-laws without a break, and with indices consistent with pink/red-noise behavior. We observed a harder-when-brighter behavior in the X-ray spectra and measured a positive correlation between VHE and X-ray fluxes with zero time lag. Such characteristics have been reported many times during flaring activity, but here they are reported for the first time in the non-flaring state. We also observed an overall anti-correlation between optical/UV and X-rays extending over the duration of the campaign. The harder-when-brighter behavior in the X-ray spectra and the measured positive X-ray/VHE correlation during the 2009 multi-wavelength campaign suggests that the physical processes dominating the emission during non-flaring states have similarities with those occurring during flaring activity. In particular, this observation supports leptonic scenarios as being responsible for the emission of Mrk421 during non-flaring activity. Such a temporally extended X-ray/VHE correlation is not driven by any single flaring event, and hence is difficult to explain within the standard hadronic scenarios. The highest variability is observed in the X-ray band, which, within the one-zone synchrotron self-Compton scenario, indicates that the electron energy distribution is most variable at the highest energies.Comment: Accepted for publication in A&A, 18 pages, 14 figures (v2 has a small modification in the acknowledgments, and also corrects a typo in the field "author" in the metadata

Functional annotation of human long noncoding RNAs via molecular phenotyping

Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-todate lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.Peer reviewe

Multifrequency Studies of the Peculiar Quasar 4C +21.35 During the 2010 Flaring Activity

The discovery of Very High Energy (VHE; E > 100 GeV) γ-ray emission from 4C +21.35 (PKS 1222+216) by MAGIC on 2010 June 17, triggered by the high activity detected by the Fermi Large Area Telescope (LAT) in high energy (HE) γ-rays, poses intriguing questions on the location of the γ-ray emitting region in this flat spectrum radio quasar (FSRQ). We present multifrequency data of 4C +21.35 collected from radio to VHE during 2010 for investigating the properties of this source and discussing a possible emission model. The first hint of detection at VHE was observed by MAGIC on 2010 May 3, soon after a γ-ray flaring activity detected by Fermi-LAT and peaking on April 29. The same emission mechanism may therefore be responsible for both the HE and VHE emission during the 2010 flaring episodes. Two optical peaks were detected on 2010 April 20 and June 30, close in time but not simultaneous with the two γ-ray peaks, while no clear correlation was observed between the X-ray and γ-ray emission. An increasing flux density was observed in radio and mm bands from the beginning of 2009, in accordance with the increasing γ-ray activity observed by Fermi-LAT, and peaking on 2011 January 27 at 230 GHz. We model the spectral energy distributions (SEDs) of 4C +21.35 for the two periods of the VHE detection and a quiescent state with a one-zone model considering the emission from a very compact region outside the broad line region. The three SEDs could be fit with a combination of synchrotron self-Compton and external Compton emission of seed photons from a dust torus, changing only the electron distribution parameters among the SEDs. The fit of the optical/UV part of the spectrum for 2010 April 29 seems to favor an inner disk radius of 3 gravitational radii, a value expected for a maximally prograde rotating Kerr black hole