Modeling Bacterial DNA: Simulation of Self-avoiding Supercoiled Worm-Like Chains Including Structural Transitions of the Helix

Under supercoiling constraints, naked DNA, such as a large part of bacterial DNA, folds into braided structures called plectonemes. The double-helix can also undergo local structural transitions, leading to the formation of denaturation bubbles and other alternative structures. Various polymer models have been developed to capture these properties, with Monte-Carlo (MC) approaches dedicated to the inference of thermodynamic properties. In this chapter, we explain how to perform such Monte-Carlo simulations, following two objectives. On one hand, we present the self-avoiding supercoiled Worm-Like Chain (ssWLC) model, which is known to capture the folding properties of supercoiled DNA, and provide a detailed explanation of a standard MC simulation method. On the other hand, we explain how to extend this ssWLC model to include structural transitions of the helix.Comment: Book chapter to appear in The Bacterial Nucleoid, Methods and Protocols, Springer serie

Seismic vulnerability and risk assessment of historic masonry buildings

Seismic risk evaluation of built-up areas involves analysis of the level of earthquake hazard of the region, building vulnerability and exposure. Within this approach that defines seismic risk, building vulnerability assessment assumes great importance, not only because of the obvious physical consequences in the eventual occurrence of a seismic event, but also because it is the one of the few potential aspects in which engineering research can intervene. In fact, rigorous vulnerability assessment of existing buildings and the implementation of appropriate retrofitting solutions can help to reduce the levels of physical damage, loss of life and the economic impact of future seismic events. Vulnerability studies of urban centresshould be developed with the aim of identifying building fragilities and reducing seismic risk. As part of the rehabilitation of the historic city centre of Coimbra, a complete identification and inspection survey of old masonry buildings has been carried out. The main purpose of this research is to discuss vulnerability assessment methodologies, particularly those of the first level, through the proposal and development of a method previously used to determine the level of vulnerability, in the assessment of physical damage and its relationship with seismic intensity

Inherent directionality explains the lack of feedback loops in empirical networks

We explore the hypothesis that the relative abundance of feedback loops in many empirical complex networks is severely reduced owing to the presence of an inherent global directionality. Aimed at quantifying this idea, we propose a simple probabilistic model in which a free parameter γ controls the degree of inherent directionality. Upon strengthening such directionality, the model predicts a drastic reduction in the fraction of loops which are also feedback loops. To test this prediction, we extensively enumerated loops and feedback loops in many empirical biological, ecological and socio-technological directed networks. We show that, in almost all cases, empirical networks have a much smaller fraction of feedback loops than network randomizations. Quite remarkably, this empirical finding is quantitatively reproduced, for all loop lengths, by our model by fitting its only parameter γ. Moreover, the fitted value of γ correlates quite well with another direct measurement of network directionality, performed by means of a novel algorithm. We conclude that the existence of an inherent network directionality provides a parsimonious quantitative explanation for the observed lack of feedback loops in empirical networks

A CLASP-modulated cell edge barrier mechanism drives cell-wide cortical microtubule organization in Arabidopsis

It is well known that the parallel order of microtubules in the plant cell cortex defines the direction of cell expansion, yet it remains unclear how microtubule orientation is controlled, especially on a cell-wide basis. Here we show through 4D imaging and computational modelling that plant cell polyhedral geometry provides spatial input that determines array orientation and heterogeneity. Microtubules depolymerize when encountering sharp cell edges head-on, whereas those oriented parallel to those sharp edges remain. Edge-induced microtubule depolymerization, however, is overcome by the microtubule-associated protein CLASP, which accumulates at specific cell edges, enables microtubule growth around sharp edges and promotes formation of microtubule bundles that span adjacent cell faces. By computationally modelling dynamic 'microtubules on a cube' with edges differentially permissive to microtubule passage, we show that the CLASP-edge complex is a 'tuneable' microtubule organizer, with the inherent flexibility to generate the numerous cortical array patterns observed in nature

Systems Biology by the Rules: Hybrid Intelligent Systems for Pathway Modeling and Discovery

Background: Expert knowledge in journal articles is an important source of data for reconstructing biological pathways and creating new hypotheses. An important need for medical research is to integrate this data with high throughput sources to build useful models that span several scales. Researchers traditionally use mental models of pathways to integrate information and development new hypotheses. Unfortunately, the amount of information is often overwhelming and these are inadequate for predicting the dynamic response of complex pathways. Hierarchical computational models that allow exploration of semi-quantitative dynamics are useful systems biology tools for theoreticians, experimentalists and clinicians and may provide a means for cross-communication. Results: A novel approach for biological pathway modeling based on hybrid intelligent systems or soft computing technologies is presented here. Intelligent hybrid systems, which refers to several related computing methods such as fuzzy logic, neural nets, genetic algorithms, and statistical analysis, has become ubiquitous in engineering applications for complex control system modeling and design. Biological pathways may be considered to be complex control systems, which medicine tries to manipulate to achieve desired results. Thus, hybrid intelligent systems may provide a useful tool for modeling biological system dynamics and computational exploration of new drug targets. A new modeling approach based on these methods is presented in the context of hedgehog regulation of the cell cycle in granule cells. Code and input files can be found at the Bionet website: www.chip.ord/~wbosl/Software/Bionet. Conclusion: This paper presents the algorithmic methods needed for modeling complicated biochemical dynamics using rule-based models to represent expert knowledge in the context of cell cycle regulation and tumor growth. A notable feature of this modeling approach is that it allows biologists to build complex models from their knowledge base without the need to translate that knowledge into mathematical form. Dynamics on several levels, from molecular pathways to tissue growth, are seamlessly integrated. A number of common network motifs are examined and used to build a model of hedgehog regulation of the cell cycle in cerebellar neurons, which is believed to play a key role in the etiology of medulloblastoma, a devastating childhood brain cancer

Wood-soil interactions in soil bioengineering slope stabilization works

In this work we propose the use of soil quality indicators with the aim of assessing the environmental impact of soil bioengineering works. This study was carried out in central Italy where soil bioengineering slope stabilization works were established using chestnut wood. In particular the goal of this study was to determine the occurrence of a wood-effect, that is changes of soil properties due to the presence of decomposing logs in two sites characterized by different time span since works setting up. The presence of the logs did not affect soil physico-chemical properties. Conversely, soil biochemical properties such as soil microbial biomass, basal and cumulative respiration activities as well as microbial indexes, were influenced by the presence of the logs confirming the role of these bioindicators as early predictors of changes occurring in soil. Although a general positive trend was observed for the biochemical properties at both sites with respect to the control soils, significant differences were recorded mainly at the site where works were established six years before soil sampling. Soil bioengineering slope stabilization works establish a positive feed-back which ultimately can benefit plants; in fact the increase in microbial mineralization activity can enhance nutrient cycling and thus promote adequate growth conditions for the plant cuttings used in the wooden-work

Soil carbon accumulation in a Populus spp. plantation supplied with high atmospheric CO2 and nitrogen fertilization

This work was carried out in the experimental area POPFACE (Tuscania, Viterbo), where a poplar short rotation forest (SRF) was treated with 550 ppm of atmospheric CO2 for six years. The experimental plots (Control and FACE) were divided in two halves, one of which was treated with nitrogen fertilization. The general aim of this research was to quantify the impact of the two rotation cycles, the CO2 enrichment and the nitrogen fertilization on: i) soil organic matter fractions more relevant for microbial metabolism; ii) microbial C mineralization activity and iii) the ecosystem capacity to store C in the soil. On soil samples collected from 2000 to 2004, the soil Organic C (TOC), the total extractable C (TEC) and several labile C fractions (MBC, WSC, ExC) were analysed. The microbial mineralization activity was also analysed. In comparison with the previous culture crop, the plantation increased the organic C storage in soil by about 23% in the second rotation cycle. Under elevated CO2, the increase of above- and belowground productivity supported a greater accumulation of labile C in soil, favouring a microbial C immobilization process. Fertilization treatment induced short-term changes in the soil C content, without overall modifications in the second rotation cycle