Visual setup of logical models of signaling and regulatory networks with ProMoT

BACKGROUND: The analysis of biochemical networks using a logical (Boolean) description is an important approach in Systems Biology. Recently, new methods have been proposed to analyze large signaling and regulatory networks using this formalism. Even though there is a large number of tools to set up models describing biological networks using a biochemical (kinetic) formalism, however, they do not support logical models. RESULTS: Herein we present a flexible framework for setting up large logical models in a visual manner with the software tool ProMoT. An easily extendible library, ProMoT's inherent modularity and object-oriented concept as well as adaptive visualization techniques provide a versatile environment. Both the graphical and the textual description of the logical model can be exported to different formats. CONCLUSION: New features of ProMoT facilitate an efficient set-up of large Boolean models of biochemical interaction networks. The modeling environment is flexible; it can easily be adapted to specific requirements, and new extensions can be introduced. ProMoT is freely available from

How needs and preferences of employees influence participation in health promotion programs: A six-month follow-up study

Background: Low participation in health promotion programs (HPPs) might hamper their effectiveness. A potential reason for low participation is disagreement between needs and preferences of potential participants and the actual HPPs offered. This study aimed to investigate employees' need and preferences for HPPs, whether these are matched by what their employers provide, and whether a higher agreement enhanced participation. Methods: Employees of two organizations participated in a six-month follow-up study (n = 738). At baseline, information was collected on employees' needs and preferences for the topic of the HPP (i.e. physical activity, healthy nutrition, smoking cessation, stress management, general health), whether they favored a HPP via their employer or at their own discretion, and their preferred HPP regarding three components with each two alternatives: mode of delivery (individual vs. group), intensity (single vs. multiple meetings), and content (assignments vs. information). Participation in HPPs was assessed at six-month

Fostering oral presentation competence through a virtual reality-based task for delivering feedback

While previous studies have stressed the importance of feedback delivered by experts, it is unclear whether students’ oral presentation competence can be fostered through innovative technology for delivering feedback. This experimental study examined the effectiveness of a virtual reality-based task, in which first-year undergraduate students practiced their presentation in a virtual environment and received feedback produced by the system, on their presentation competence components (i.e. cognition, behaviour and attitudes towards presenting). The effects were compared with a control condition, which was a face-to-face presentation task with expert feedback. The students’ performance was measured using pre- and post-test multiple-choice tests, validated rubrics, and self-evaluation instruments. Results revealed significant improvements from pre-test to post-test in all three presentation competence components, without a difference between the conditions. Furthermore, the self-evaluation tests showed that students who presented in virtual reality were appreciative of the detailed and analytical feedback they received. Because of sample size limitations, the effects found could not be generalised. Therefore, future research on a larger sample is needed to examine population effects. Follow-up studies should focus on the extent to which virtual reality-based tasks can encourage self-regulation skills for the effective and efficient integration of these tasks in presentation courses.</p

Assessing microbial competition in a hydrogen‐based membrane biofilm reactor (MBfR) using multidimensional modeling

The membrane biofilm reactor (MBfR) is a novel technology that safely delivers hydrogen to the base of a denitrifying biofilm via gas‐supplying membranes. While hydrogen is an effective electron donor for denitrifying bacteria (DNB), it also supports sulfate‐reducing bacteria (SRB) and methanogens (MET), which consume hydrogen and create undesirable by‐products. SRB and MET are only competitive for hydrogen when local nitrate concentrations are low, therefore SRB and MET primarily grow near the base of the biofilm. In an MBfR, hydrogen concentrations are greatest at the base of the biofilm, making SRB and MET more likely to proliferate in an MBfR system than a conventional biofilm reactor. Modeling results showed that because of this, control of the hydrogen concentration via the intramembrane pressure was a key tool for limiting SRB and MET development. Another means is biofilm management, which supported both sloughing and erosive detachment. For the conditions simulated, maintaining thinner biofilms promoted higher denitrification fluxes and limited the presence of SRB and MET. The 2‐d modeling showed that periodic biofilm sloughing helped control slow‐growing SRB and MET. Moreover, the rough (non‐flat) membrane assembly in the 2‐d model provided a special niche for SRB and MET that was not represented in the 1‐d model. This study compared 1‐d and 2‐d biofilm model applicability for simulating competition in counter‐diffusional biofilms. Although more computationally expensive, the 2‐d model captured important mechanisms unseen in the 1‐d model. Biotechnol. Bioeng. 2015;112: 1843–1853. © 2015 Wiley Periodicals, Inc.Competition between denitrifying (DNB) and undesirable sulfate‐reducing bacteria (SRB) and methanogens (MET) were evaluated in a hydrogen‐based, membrane biofilm reactor (MBfR) through 1‐d and 2‐d biofilm modeling studies. The 2‐d model allowed novel mechanisms, not previously described for MBfRs, to be captured.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112211/1/bit25607.pd

SBML Level 3 Package Specification: Hierarchical Model Composition

In the context of SBML, “hierarchical model composition” refers to the ability to include models as submodels inside another model. The goal is to support the ability of modelers and software tools to do such things as (1) decompose larger models into smaller ones, as a way to manage complexity; (2) incorporate multiple instances of a given model within one or more enclosing models, to avoid literal duplication of repeated elements; and (3) create libraries of reusable, tested models, much as is done in software development and other engineering fields. SBML Level 3 Version 1 Core (Hucka et al., 2010), by itself, has no direct support for allowing a model to include other models as submodels. Software tools either have to implement their own schemes outside of SBML, or (in principle) could use annotations to augment a plain SBML Level 3 model with the necessary information to allow a software tool to compose a model out of submodels. However, such solutions would be proprietary and tool-specific, and not conducive to interoperability. There is a clear need for an official SBML language facility for hierarchical model composition. This document describes a specification for an SBML Level 3 package that provides exactly such a facility

Accurate detection of circulating tumor DNA using nanopore consensus sequencing

Levels of circulating tumor DNA (ctDNA) in liquid biopsies may serve as a sensitive biomarker for real-time, minimally-invasive tumor diagnostics and monitoring. However, detecting ctDNA is challenging, as much fewer than 5% of the cell-free DNA in the blood typically originates from the tumor. To detect lowly abundant ctDNA molecules based on somatic variants, extremely sensitive sequencing methods are required. Here, we describe a new technique, CyclomicsSeq, which is based on Oxford Nanopore sequencing of concatenated copies of a single DNA molecule. Consensus calling of the DNA copies increased the base-calling accuracy ~60×, enabling accurate detection of TP53 mutations at frequencies down to 0.02%. We demonstrate that a TP53-specific CyclomicsSeq assay can be successfully used to monitor tumor burden during treatment for head-and-neck cancer patients. CyclomicsSeq can be applied to any genomic locus and offers an accurate diagnostic liquid biopsy approach that can be implemented in clinical workflows

Author Correction: Accurate detection of circulating tumor DNA using nanopore consensus sequencing

The Data Availability statement in the original version of the paper reads: “The sequencing datasets generated during the current study are available upon request at EGA, under accession number EGAS00001003759”. However, as this data upload was not successful, the authors reuploaded the data under a different accession number and have amended the Data Availability statement to read “The sequencing datasets generated during the current study are available upon request at EGA, under accession number EGAS00001007090”. The original article has been corrected.</p

Arabidopsis is susceptible to the cereal ear blight fungal pathogens Fusarium graminearum and Fusarium culmorum

The fungal pathogens Fusarium graminearum and F. culmorum cause ear blight disease on cereal crops worldwide. The disease lowers both grain quality and grain safety. Disease prevalence is increasing due to changes in cropping practices and the difficulties encountered by plant breeders when trying to introgress the polygene-based resistance. The molecular basis of resistance to Fusarium ear blight in cereal species is poorly understood. This is primarily due to the large size of cereal genomes and the expensive resources required to undertake gene function studies in cereals. We therefore explored the possibility of developing various model floral infection systems that would be more amenable to experimental manipulation and high-throughput gene function studies. The floral tissues of tobacco, tomato, soybean and Arabidopsis were inoculated with Fusarium conidia and this resulted in disease symptoms on anthers, anther filaments and petals in each plant species. However, only in Arabidopsis did this initial infection then spread into the developing siliques and seeds. A survey of 236 Arabidopsis ecotypes failed to identify a single genotype that was extremely resistant or susceptible to Fusarium floral infections. Three Arabidopsis floral mutants that failed to develop anthers and/or functional pollen (i.e. agamous-1, apetala1-3 and dad1 ) were significantly less susceptible to Fusarium floral infection than wild type. Deoxynivalenol (DON) mycotoxin production was also detected in Fusarium -infected flowers at >1 ppm. This novel floral pathosystem for Arabidopsis appears to be highly representative of a serious cereal crop disease

Marine spatial planning: risk or opportunity for fisheries in the North Sea?

The North Sea is one of the busiest marine areas in the world. It is also a major fisheries ground. Bordered by seven countries with their own spatial uses and claims, the stage is set for complex and demanding governance challenges. Recent decades have also seen user groups multiply, competition for space and resources increase, and the pressure on the marine environment and its living natural resources grow. As governments strive to balance conservation and economic development needs, they also have to deal with inter-as well as intra-national user conflicts. Marine Spatial Planning (MSP) has arrived as a new approach to these issues. It is argued that for North Sea fishing people and their communities MSP holds risks as well as opportunities, depending on which institutions are formed and what role they are allowed to play in the planning process

A novel family of diversified immunoregulatory receptors in teleosts is homologous to both mammalian Fc receptors and molecules encoded within the leukocyte receptor complex

Three novel and closely related leukocyte immune-type receptors (IpLITR) have been identified in channel catfish (Ictalurus punctatus). These receptors belong to a large polymorphic and polygenic subset of the Ig superfamily with members located on at least three independently segregating loci. Like mammalian and avian innate immune regulatory receptors, IpLITRs have both putative inhibitory and stimulatory forms, with multiple types coexpressed in various lymphoid tissues and clonal leukocyte cell lines. IpLITRs have an unusual and novel relationship to mammalian and avian innate immune receptors: the membrane distal Ig domains of an individual IpLITR are related to fragment crystallizable receptors (FcRs) and FcR-like proteins, whereas the membrane proximal Ig domains are related to several leukocyte receptor complex encoded receptors. This unique composition of Ig domains within individual receptors supports the hypothesis that functionally and genomically distinct immune receptor families found in tetrapods may have evolved from such ancestral genes by duplication and recombination events. Furthermore, the discovery of a large heterogeneous family of immunoregulatory receptors in teleosts, reminiscent of amphibian, avian, and mammalian Ig-like receptors, suggests that complex innate immune receptor networks have been conserved during vertebrate evolution. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at http://dx.doi.org/10.1007/s00251-006-0134-1 and is accessible for authorized users