Application of regulatory sequence analysis and metabolic network analysis to the interpretation of gene expression data

We present two complementary approaches for the interpretation of clusters of co-regulated genes, such as those obtained from DNA chips and related methods. Starting from a cluster of genes with similar expression profiles, two basic questions can be asked: 1. Which mechanism is responsible for the coordinated transcriptional response of the genes? This question is approached by extracting motifs that are shared between the upstream sequences of these genes. The motifs extracted are putative cis-acting regulatory elements. 2. What is the physiological meaning for the cell to express together these genes? One way to answer the question is to search for potential metabolic pathways that could be catalyzed by the products of the genes. This can be done by selecting the genes from the cluster that code for enzymes, and trying to assemble the catalyzed reactions to form metabolic pathways. We present tools to answer these two questions, and we illustrate their use with selected examples in the yeast Saccharomyces cerevisiae. The tools are available on the web (http://ucmb.ulb.ac.be/bioinformatics/rsa-tools/; http://www.ebi.ac.uk/research/pfbp/; http://www.soi.city.ac.uk/~msch/)

RSAT 2011: regulatory sequence analysis tools

RSAT (Regulatory Sequence Analysis Tools) comprises a wide collection of modular tools for the detection of cis-regulatory elements in genome sequences. Thirteen new programs have been added to the 30 described in the 2008 NAR Web Software Issue, including an automated sequence retrieval from EnsEMBL (retrieve-ensembl-seq), two novel motif discovery algorithms (oligo-diff and info-gibbs), a 100-times faster version of matrix-scan enabling the scanning of genome-scale sequence sets, and a series of facilities for random model generation and statistical evaluation (random-genome-fragments, random-motifs, random-sites, implant-sites, sequence-probability, permute-matrix). Our most recent work also focused on motif comparison (compare-matrices) and evaluation of motif quality (matrix-quality) by combining theoretical and empirical measures to assess the predictive capability of position-specific scoring matrices. To process large collections of peak sequences obtained from ChIP-seq or related technologies, RSAT provides a new program (peak-motifs) that combines several efficient motif discovery algorithms to predict transcription factor binding motifs, match them against motif databases and predict their binding sites. Availability (web site, stand-alone programs and SOAP/WSDL (Simple Object Access Protocol/Web Services Description Language) web services): http://rsat.ulb.ac.be/rsat/

Use and non-use of accounting information: The case of controversial projects in public and non-profit settings

This paper investigates whether and how accounting information is used in debates and decision-making processes about controversial projects in public sector and non-profit settings in the Netherlands and Italy. The research is based on two case studies and relies on multiple methods of qualitative data collection, including documents, interviews with key actors and media reports. The research finds a more limited extent of accounting information use than expected given the controversiality of the projects. It raises various types of explanations for this limited accounting information use, especially that ruling groups of actors supporting the project do not give room to the opposing minority for putting forward their concerns and preferences. The power position of the ruling majority thus matters in mitigating opportunities for a dialogic use of accounting information leading to the decision-making about the projects. So, controversiality is a determining factor, but insufficient as an explanation for the extent to which accounting information is used. In addition, the type of accounting information use is depending on the actors’ appreciation of the project. Advocates and opponents concerning both projects were in general inclined to an ammunition type of accounting information use, whereas actors holding a neutral position used available accounting information in a more rational way.This paper investigates whether and how accounting information is used in debates and decision-making processes about controversial projects in public sector and non-profit settings in the Netherlands and Italy. The research is based on two case studies and relies on multiple methods of qualitative data collection, including documents, interviews with key actors and media reports. The research finds a more limited extent of accounting information use than expected given the controversiality of the projects. It raises various types of explanations for this limited accounting information use, especially that ruling groups of actors supporting the project do not give room to the opposing minority for putting forward their concerns and preferences. The power position of the ruling majority thus matters in mitigating opportunities for a dialogic use of accounting information leading to the decision-making about the projects. So, controversiality is a determining factor, but insufficient as an explanation for the extent to which accounting information is used. In addition, the type of accounting information use is depending on the actors’ appreciation of the project. Advocates and opponents concerning both projects were in general inclined to an ammunition type of accounting information use, whereas actors holding a neutral position used available accounting information in a more rational way

Downregulation of Fzd6 and Cthrc1 and upregulation of olfactory receptors and protocadherins by dietary beta-carotene in lungs of Bcmo1-/- mice.

An ongoing controversy exists on beneficial versus harmful effects of high beta-carotene (BC) intake, especially for the lung. To elucidate potential mechanisms, we studied effects of BC on lung gene expression. We used a beta-carotene 15,15'-monooxygenase 1 (Bcmo1) knockout mouse (Bcmo1-/-) model, unable to convert BC to retinoids, and wild-type mice (Bcmo1+/+) mice to dissect the effects of intact BC from effects of BC metabolites. As expected, BC supplementation resulted in a higher BC accumulation in lungs of Bcmo1-/- mice than in lungs of Bcmo1+/+ mice. Whole mouse genome transcriptome analysis on lung tissue revealed that more genes were regulated in Bcmo1-/- mice than Bcmo1+/+ mice upon BC supplementation. Frizzled homolog 6 (Fzd6) and collagen triple helix repeat containing 1 (Cthrc1) were significantly downregulated (fold changes -2.99 and -2.60, respectively, false discovery rate <0.05) by BC in Bcmo1-/-. Moreover, many olfactory receptors and many members of the protocadherin family were upregulated. Since both olfactory receptors and protocadherins have an important function in sensory nerves and Fzd6 and Cthrc1 are important in stem cell development, we hypothesize that BC might have an effect on the highly innervated pulmonary neuroendocrine cell (PNEC) cluster. PNECs are highly associated with sensory nerves and are important cells in the control of stem cells. A role for BC in the innervated PNEC cluster might be of particular importance in smoke-induced carcinogenesis since PNEC-derived lung cancer is highly associated with tobacco smoke

Downregulation of Fzd6 and Cthrc1 and upregulation of olfactory receptors and protocadherins by dietary beta-carotene in lungs of Bcmo1-/- mice.

An ongoing controversy exists on beneficial versus harmful effects of high beta-carotene (BC) intake, especially for the lung. To elucidate potential mechanisms, we studied effects of BC on lung gene expression. We used a beta-carotene 15,15'-monooxygenase 1 (Bcmo1) knockout mouse (Bcmo1-/-) model, unable to convert BC to retinoids, and wild-type mice (Bcmo1+/+) mice to dissect the effects of intact BC from effects of BC metabolites. As expected, BC supplementation resulted in a higher BC accumulation in lungs of Bcmo1-/- mice than in lungs of Bcmo1+/+ mice. Whole mouse genome transcriptome analysis on lung tissue revealed that more genes were regulated in Bcmo1-/- mice than Bcmo1+/+ mice upon BC supplementation. Frizzled homolog 6 (Fzd6) and collagen triple helix repeat containing 1 (Cthrc1) were significantly downregulated (fold changes -2.99 and -2.60, respectively, false discovery rate <0.05) by BC in Bcmo1-/-. Moreover, many olfactory receptors and many members of the protocadherin family were upregulated. Since both olfactory receptors and protocadherins have an important function in sensory nerves and Fzd6 and Cthrc1 are important in stem cell development, we hypothesize that BC might have an effect on the highly innervated pulmonary neuroendocrine cell (PNEC) cluster. PNECs are highly associated with sensory nerves and are important cells in the control of stem cells. A role for BC in the innervated PNEC cluster might be of particular importance in smoke-induced carcinogenesis since PNEC-derived lung cancer is highly associated with tobacco smoke

Tunability of Critical Casimir Interactions by Boundary Conditions

We experimentally demonstrate that critical Casimir forces in colloidal systems can be continuously tuned by the choice of boundary conditions. The interaction potential of a colloidal particle in a mixture of water and 2,6-lutidine has been measured above a substrate with a gradient in its preferential adsorption properties for the mixture's components. We find that the interaction potentials at constant temperature but different positions relative to the gradient continuously change from attraction to repulsion. This demonstrates that critical Casimir forces respond not only to minute temperature changes but also to small changes in the surface properties.Comment: 4 figures; http://www.iop.org/EJ/article/0295-5075/88/2/26001/epl_88_2_26001.htm

New development: The ethics of accounting information manipulation in the political arena

ABSTRACT This article explores ethical issues of accounting information manipulation (AIM) in the political arena. After conceptualizing AIM, including its drivers, techniques, contextualities and impacts, the authors discuss underlying tensions between various types of values that emerge as a trigger for applying AIM. In that respect a distinction is made between values at the societal, organizational and individual level, such as, respectively, sustainability, transparency and honesty, and additionally between private values related to personal gain and public values

Generalized Newton-Cartan geometries for particles and strings

We discuss the generalized Newton-Cartan geometries that can serve as gravitational background fields for particles and strings. In order to enable us to define affine connections that are invariant under all the symmetries of the structure group, we describe torsionful geometries with independent torsion tensors. A characteristic feature of the non-Lorentzian geometries we consider is that some of the torsion tensors are so-called ‘intrinsic torsion’ tensors. Setting some components of these intrinsic torsion tensors to zero leads to constraints on the geometry. For both particles and strings, we discuss various such constraints that can be imposed consistently with the structure group symmetries. In this way, we reproduce several results in the literature.</p

The First Three Rungs of the Cosmological Distance Ladder

It is straightforward to determine the size of the Earth and the distance to the Moon without making use of a telescope. The methods have been known since the 3rd century BC. However, few amateur or professional astronomers have worked this out from data they themselves have taken. Here we use a gnomon to determine the latitude and longitude of South Bend, Indiana, and College Station, Texas, and determine a value of the radius of the Earth of 6290 km, only 1.4 percent smaller than the true value. We use the method of Aristarchus and the size of the Earth's shadow during the lunar eclipse of 2011 June 15 to derive an estimate of the distance to the Moon (62.3 R_Earth), some 3.3 percent greater than the true mean value. We use measurements of the angular motion of the Moon against the background stars over the course of two nights, using a simple cross staff device, to estimate the Moon's distance at perigee and apogee. Finally, we use simultaneous CCD observations of asteroid 1996 HW1 obtained with small telescopes in Socorro, New Mexico, and Ojai, California, to derive a value of the Astronomical Unit of (1.59 +/- 0.19) X 10^8 km, about 6 percent too large. The data and methods presented here can easily become part of a beginning astronomy lab class.Comment: 34 pages, 11 figures, accepted for publication in American Journal of Physic