PKSB1740-517: An ALMA view of the cold gas feeding a distant interacting young radio galaxy

Cold neutral gas is a key ingredient for growing the stellar and central black hole mass in galaxies throughout cosmic history. We have used the Atacama Large Millimetre Array (ALMA) to detect a rare example of redshifted $^{12}$CO(2-1) absorption in PKS B1740-517, a young ($t \sim 1.6 \times 10^{3}$ yr) and luminous ($L_{\rm 5 GHz} \sim 6.6 \times 10^{43}$ erg s$^{-1}$ ) radio galaxy at $z = 0.44$ that is undergoing a tidal interaction with at least one lower-mass companion. The coincident HI 21-cm and molecular absorption have very similar line profiles and reveal a reservoir of cold gas ($M_{\rm gas} \sim 10^{7} - 10^{8}$ M$_{\odot}$), likely distributed in a disc or ring within a few kiloparsecs of the nucleus. A separate HI component is kinematically distinct and has a very narrow line width ($\Delta{v}_{\rm FWHM} \lesssim 5$ km s$^{-1}$), consistent with a single diffuse cloud of cold ($T_{\rm k} \sim 100$ K) atomic gas. The $^{12}$CO(2-1) absorption is not associated with this component, which suggests that the cloud is either much smaller than 100 pc along our sight-line and/or located in low-metallicity gas that was possibly tidally stripped from the companion. We argue that the gas reservoir in PKS B1740-517 may have accreted onto the host galaxy $\sim$50 Myr before the young radio AGN was triggered, but has only recently reached the nucleus. This is consistent with the paradigm that powerful luminous radio galaxies are triggered by minor mergers and interactions with low-mass satellites and represent a brief, possibly recurrent, active phase in the life cycle of massive early type galaxies.Comment: 15 pages, 7 figures, accepted for publication in MNRA

The frontiers of participatory public engagement

Currently missing from critical literature on public engagement with academic research is a public-centric analysis of the wider contemporary context of developments in the field of public engagement and participation. Drawing on three differently useful strands of the existing theoretical literature on the public, this article compares a diverse sample of 100 participatory public engagement initiatives in order to first, analyse a selection of the myriad ways that the public is being constituted and supported across this contemporary field and second, identify what socio-cultural researchers might learn from these developments. Emerging from this research is a preliminary map of the field of public engagement and participation. This map highlights relationships and divergences that exist among diverse forms of practice and brings into clearer view a set of tensions between different contemporary approaches to public engagement and participation. Two ‘frontiers’ of participatory public engagement that socio-cultural researchers should attend are also identified. At the first, scholars need to be critical regarding the particular versions of the public that their preferred approach to engagement and participation supports and concerning how their specific identifications with the public relate to those being addressed across the wider field. At the second frontier, researchers need to consider the possibilities for political intervention that public engagement and participation practice could open out, both in the settings they are already working and also in the much broader, rapidly developing and increasingly complicated contemporary field of public engagement and participation that this article explores

Winnowing DNA for Rare Sequences: Highly Specific Sequence and Methylation Based Enrichment

Rare mutations in cell populations are known to be hallmarks of many diseases and cancers. Similarly, differential DNA methylation patterns arise in rare cell populations with diagnostic potential such as fetal cells circulating in maternal blood. Unfortunately, the frequency of alleles with diagnostic potential, relative to wild-type background sequence, is often well below the frequency of errors in currently available methods for sequence analysis, including very high throughput DNA sequencing. We demonstrate a DNA preparation and purification method that through non-linear electrophoretic separation in media containing oligonucleotide probes, achieves 10,000 fold enrichment of target DNA with single nucleotide specificity, and 100 fold enrichment of unmodified methylated DNA differing from the background by the methylation of a single cytosine residue

FISim: A new similarity measure between transcription factor binding sites based on the fuzzy integral

Background Regulatory motifs describe sets of related transcription factor binding sites (TFBSs) and can be represented as position frequency matrices (PFMs). De novo identification of TFBSs is a crucial problem in computational biology which includes the issue of comparing putative motifs with one another and with motifs that are already known. The relative importance of each nucleotide within a given position in the PFMs should be considered in order to compute PFM similarities. Furthermore, biological data are inherently noisy and imprecise. Fuzzy set theory is particularly suitable for modeling imprecise data, whereas fuzzy integrals are highly appropriate for representing the interaction among different information sources.Results We propose FISim, a new similarity measure between PFMs, based on the fuzzy integral of the distance of the nucleotides with respect to the information content of the positions. Unlike existing methods, FISim is designed to consider the higher contribution of better conserved positions to the binding affinity. FISim provides excellent results when dealing with sets of randomly generated motifs, and outperforms the remaining methods when handling real datasets of related motifs. Furthermore, we propose a new cluster methodology based on kernel theory together with FISim to obtain groups of related motifs potentially bound by the same TFs, providing more robust results than existing approaches.Conclusion FISim corrects a design flaw of the most popular methods, whose measures favour similarity of low information content positions. We use our measure to successfully identify motifs that describe binding sites for the same TF and to solve real-life problems. In this study the reliability of fuzzy technology for motif comparison tasks is proven.This work has been carried out as part of projects P08-TIC-4299 of J. A., Sevilla and TIN2006-13177 of DGICT, Madrid

Nucleosome-coupled expression differences in closely-related species

<p>Abstract</p> <p>Background</p> <p>Genome-wide nucleosome occupancy is negatively related to the average level of transcription factor motif binding based on studies in yeast and several other model organisms. The degree to which nucleosome-motif interactions relate to phenotypic changes across species is, however, unknown.</p> <p>Results</p> <p>We address this challenge by generating nucleosome positioning and cell cycle expression data for <it>Saccharomyces bayanus </it>and show that differences in nucleosome occupancy reflect cell cycle expression divergence between two yeast species, <it>S. bayanus </it>and <it>S. cerevisiae</it>. Specifically, genes with nucleosome-depleted MBP1 motifs upstream of their coding sequence show periodic expression during the cell cycle, whereas genes with nucleosome-shielded motifs do not. In addition, conserved cell cycle regulatory motifs across these two species are more nucleosome-depleted compared to those that are not conserved, suggesting that the degree of conservation of regulatory sites varies, and is reflected by nucleosome occupancy patterns. Finally, many changes in cell cycle gene expression patterns across species can be correlated to changes in nucleosome occupancy on motifs (rather than to the presence or absence of motifs).</p> <p>Conclusions</p> <p>Our observations suggest that alteration of nucleosome occupancy is a previously uncharacterized feature related to the divergence of cell cycle expression between species.</p

Molecular mechanisms of EGF signaling-dependent regulation of pipe, a gene crucial for dorsoventral axis formation in Drosophila

During Drosophila oogenesis the expression of the sulfotransferase Pipe in ventral follicle cells is crucial for dorsoventral axis formation. Pipe modifies proteins that are incorporated in the ventral eggshell and activate Toll signaling which in turn initiates embryonic dorsoventral patterning. Ventral pipe expression is the result of an oocyte-derived EGF signal which down-regulates pipe in dorsal follicle cells. The analysis of mutant follicle cell clones reveals that none of the transcription factors known to act downstream of EGF signaling in Drosophila is required or sufficient for pipe regulation. However, the pipe cis-regulatory region harbors a 31-bp element which is essential for pipe repression, and ovarian extracts contain a protein that binds this element. Thus, EGF signaling does not act by down-regulating an activator of pipe as previously suggested but rather by activating a repressor. Surprisingly, this repressor acts independent of the common co-repressors Groucho or CtBP

Interferon Regulatory Factor 8 Regulates Pathways for Antigen Presentation in Myeloid Cells and during Tuberculosis

IRF8 (Interferon Regulatory Factor 8) plays an important role in defenses against intracellular pathogens, including several aspects of myeloid cells function. It is required for ontogeny and maturation of macrophages and dendritic cells, for activation of anti-microbial defenses, and for production of the Th1-polarizing cytokine interleukin-12 (IL-12) in response to interferon gamma (IFNγ) and protection against infection with Mycobacterium tuberculosis. The transcriptional programs and cellular pathways that are regulated by IRF8 in response to IFNγ and that are important for defenses against M. tuberculosis are poorly understood. These were investigated by transcript profiling and chromatin immunoprecipitation on microarrays (ChIP-chip). Studies in primary macrophages identified 368 genes that are regulated by IRF8 in response to IFNγ/CpG and that behave as stably segregating expression signatures (eQTLs) in F2 mice fixed for a wild-type or mutant allele at IRF8. A total of 319 IRF8 binding sites were identified on promoters genome-wide (ChIP-chip) in macrophages treated with IFNγ/CpG, defining a functional G/AGAAnTGAAA motif. An analysis of the genes bearing a functional IRF8 binding site, and showing regulation by IFNγ/CpG in macrophages and/or in M. tuberculosis-infected lungs, revealed a striking enrichment for the pathways of antigen processing and presentation, including multiple structural and enzymatic components of the Class I and Class II MHC (major histocompatibility complex) antigen presentation machinery. Also significantly enriched as IRF8 targets are the group of endomembrane- and phagosome-associated small GTPases of the IRG (immunity-related GTPases) and GBP (guanylate binding proteins) families. These results identify IRF8 as a key regulator of early response pathways in myeloid cells, including phagosome maturation, antigen processing, and antigen presentation by myeloid cells

Cognitive and psychological science insights to improve climate change data visualization

Visualization of climate data plays an integral role in the communication of climate change findings to both expert and non-expert audiences. The cognitive and psychological sciences can provide valuable insights into how to improve visualization of climate data based on knowledge of how the human brain processes visual and linguistic information. We review four key research areas to demonstrate their potential to make data more accessible to diverse audiences: directing visual attention, visual complexity, making inferences from visuals, and the mapping between visuals and language. We present evidence-informed guidelines to help climate scientists increase the accessibility of graphics to non-experts, and illustrate how the guidelines can work in practice in the context of Intergovernmental Panel on Climate Change graphics

Gene co-regulation by Fezf2 selects neurotransmitter identity and connectivity of corticospinal neurons

The neocortex contains an unparalleled diversity of neuronal subtypes, each defined by distinct traits that are developmentally acquired under the control of subtype-specific and pan-neuronal genes. The regulatory logic that orchestrates the expression of these unique combinations of genes is unknown for any class of cortical neuron. Here, we report that Fezf2 is a selector gene able to regulate the expression of gene sets that collectively define mouse corticospinal motor neurons (CSMN). We find that Fezf2 directly induces the glutamatergic identity of CSMN via activation of Vglut1 (Slc17a7) and inhibits a GABAergic fate by repressing transcription of Gad1. In addition, we identify the axon guidance receptor EphB1 as a target of Fezf2 necessary to execute the ipsilateral extension of the corticospinal tract. Our data indicate that co-regulated expression of neuron subtype–specific and pan-neuronal gene batteries by a single transcription factor is one component of the regulatory logic responsible for the establishment of CSMN identity

In Silico Simulation of Corticosteroids Effect on an NFkB- Dependent Physicochemical Model of Systemic Inflammation

During the onset of an inflammatory response signaling pathways are activated for "translating" extracellular signals into intracellular responses converging to the activation of nuclear factor (NF)-kB, a central transcription factor in driving the inflammatory response. An inadequate control of its transcriptional activity is associated with the culmination of a hyper-inflammatory response making it a desired therapeutic target. Predicated upon the nature of the response, a systems level analysis might provide rational leads for the development of strategies that promote the resolution of the response.A physicochemical host response model is proposed to integrate biological information in the form of kinetic rules and signaling cascades with pharmacokinetic models of drug action for the modulation of the response. The unifying hypothesis is that the response is triggered by the activation of the NFkB signaling module and corticosteroids serve as a template for assessing anti-inflammatory strategies. The proposed in silico model is evaluated through its ability to predict and modulate uncontrolled responses. The pre-exposure of the system to hypercortisolemia, i.e. 6 hr before or simultaneously with the infectious challenge "reprograms" the dynamics of the host towards a balanced inflammatory response. However, if such an intervention occurs long before the inflammatory insult a symptomatic effect is observed instead of a protective relief while a steroid infusion after inducing inflammation requires much higher drug doses.We propose a reversed engineered inflammation model that seeks to describe how the system responds to a multitude of external signals. Timing of intervention and dosage regimes appears to be key determinants for the protective or symptomatic effect of exogenous corticosteroids. Such results lie in qualitative agreement with in vivo human studies exposed both to LPS and corticosteroids under various time intervals thus improving our understanding of how interacting modules generate a behavior