Modularization for the Cell Ontology

One of the premises of the OBO Foundry is that development of an orthogonal set of ontologies will increase domain expert contributions and logical interoperability, and decrease maintenance workload. For these reasons, the Cell Ontology (CL) is being re-engineered. This process requires the extraction of sub-modules from existing OBO ontologies, which presents a number of practical engineering challenges. These extracted modules may be intended to cover a narrow or a broad set of species. In addition, applications and resources that make use of the Cell Ontology have particular modularization requirements, such as the ability to extract custom subsets or unions of the Cell Ontology with other OBO ontologies. These extracted modules may be intended to cover a narrow or a broad set of species, which presents unique complications.

We discuss some of these requirements, and present our progress towards a customizable simple-to-use modularization tool that leverages existing OWL-based tools and opens up their use for the CL and other ontologies

Constraining the Nature of X-ray Cavities in Clusters and Galaxies

We present results from an extensive survey of 64 cavities in the X-ray halos of clusters, groups and normal elliptical galaxies. We show that the evolution of the size of the cavities as they rise in the X-ray atmosphere is inconsistent with the standard model of adiabatic expansion of purely hydrodynamic models. We also note that the majority of the observed bubbles should have already been shredded apart by Rayleigh-Taylor and Richtmyer-Meshkov instabilities if they were of purely hydrodynamic nature. Instead we find that the data agrees much better with a model where the cavities are magnetically dominated and inflated by a current-dominated magneto-hydrodynamic jet model, recently developed by Li et al. (2006) and Nakamura et al. (2006). We conduct complex Monte-Carlo simulations of the cavity detection process including incompleteness effects to reproduce the cavity sample's characteristics. We find that the current-dominated model agrees within 1sigma, whereas the other models can be excluded at >5sigma confidence. To bring hydrodynamic models into better agreement, cavities would have to be continuously inflated. However, these assessments are dependent on our correct understanding of the detectability of cavities in X-ray atmospheres, and will await confirmation when automated cavity detection tools become available in the future. Our results have considerable impact on the energy budget associated with active galactic nucleus feedback.Comment: 21 pages, 12 figures, emulateapj, accepted for publication in ApJ, responded to referee's comments and added a new model, conclusions unchange

A search for radioactive 26Al in the nova-like variable V4332 Sagittarii

We have searched for the important radioactive isotope 26Al in the nova-like source V4332 Sgr. Recent results from gamma ray astronomy show that there is pervasive emission of the 1.809 MeV gamma ray photon, arising from the decay of 26Al to 26Mg, from all over the galactic plane. Though the sites from where this emission originates are not clearly established, novae are believed to be an important contributing source. In this context, V4332 Sgr presented a rare opportunity to observationally investigate whether novae or novae-like sources synthesize 26Al and to what extent. Strong AlO bands in the near-IR have been reported in this object recently. As molecular bands of different isotopic compositions are readily resolved spectroscopically (e.g. 12CO and 13CO), it was thought that the components of AlO associated with 26Al and stable 27Al could be detected as separate bands. Our spectra indicate that there is no strong presence of 26Al in V4332 Sgr. A reliable upper limit of 0.10 for the 26Al/27Al ratio is determined which constitutes the first observational constraint for this ratio in a potential 26Al producing source. While V4332 Sgr is not a typical nova, its outburst amplitude and light-curve behaviour bear close similarity to that of novae. Hence, although the results from V4332 Sgr cannot be directly extended to novae in general, the limit on the observed 26Al/27Al ratio could be a useful input in constraining rather uncertain nucleosynthesis models for the production of 26Al in novae/novae-like sources. By comparing the observed 26Al/27Al ratio in V4332 Sgr with that expected in classical novae it appears unlikely that the progenitor of V4332 Sgr is an Oxygen-Neon-Magnesium white dwarf.Comment: 9 pages, 2 figures, to appear in Ap.J(L) July 200

Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice.

Oxidized phospholipids (OxPL) are ubiquitous, are formed in many inflammatory tissues, including atherosclerotic lesions, and frequently mediate proinflammatory changes 1 . Because OxPL are mostly the products of non-enzymatic lipid peroxidation, mechanisms to specifically neutralize them are unavailable and their roles in vivo are largely unknown. We previously cloned the IgM natural antibody E06, which binds to the phosphocholine headgroup of OxPL, and blocks the uptake of oxidized low-density lipoprotein (OxLDL) by macrophages and inhibits the proinflammatory properties of OxPL2-4. Here, to determine the role of OxPL in vivo in the context of atherogenesis, we generated transgenic mice in the Ldlr-/- background that expressed a single-chain variable fragment of E06 (E06-scFv) using the Apoe promoter. E06-scFv was secreted into the plasma from the liver and macrophages, and achieved sufficient plasma levels to inhibit in vivo macrophage uptake of OxLDL and to prevent OxPL-induced inflammatory signalling. Compared to Ldlr-/- mice, Ldlr -/- E06-scFv mice had 57-28% less atherosclerosis after 4, 7 and even 12 months of 1% high-cholesterol diet. Echocardiographic and histologic evaluation of the aortic valves demonstrated that E06-scFv ameliorated the development of aortic valve gradients and decreased aortic valve calcification. Both cholesterol accumulation and in vivo uptake of OxLDL were decreased in peritoneal macrophages, and both peritoneal and aortic macrophages had a decreased inflammatory phenotype. Serum amyloid A was decreased by 32%, indicating decreased systemic inflammation, and hepatic steatosis and inflammation were also decreased. Finally, the E06-scFv prolonged life as measured over 15 months. Because the E06-scFv lacks the functional effects of an intact antibody other than the ability to bind OxPL and inhibit OxLDL uptake in macrophages, these data support a major proatherogenic role of OxLDL and demonstrate that OxPL are proinflammatory and proatherogenic, which E06 counteracts in vivo. These studies suggest that therapies inactivating OxPL may be beneficial for reducing generalized inflammation, including the progression of atherosclerosis, aortic stenosis and hepatic steatosis

A Chandra Study of the Radio Galaxy NGC 326: Wings, Outburst History, and AGN Feedback

NGC 326 is one of the most prominent X- or Z-shaped radio galaxies (XRGs/ZRGs) and has been the subject of several studies attempting to explain its morphology through either fluid motions or reorientation of the jet axis. We examine a 100 ks archival Chandra exposure and find several features associated with the radio galaxy: a high-temperature front that may indicate a shock, high-temperature knots around the rim of the radio emission, and a cavity associated with the eastern wing of the radio galaxy. A reasonable interpretation of these features in light of the radio data allows us to reconstruct the history of the AGN outbursts. The active outburst was likely once a powerful radio source which has since decayed, and circumstantial evidence favors reorientation as the means to produce the wings. Because of the obvious interaction between the radio galaxy and the ICM and the wide separation between the active lobes and wings, we conclude that XRGs are excellent sources in which to study AGN feedback in galaxy groups by measuring the heating rates associated with both active and passive heating mechanisms.Comment: 13 pages, 8 figures, Accepted by Ap

Diminished circadian and ultradian rhythms in pathological brain tissue in human in vivo

Chronobiological rhythms, such as the circadian rhythm, have long been linked to neurological disorders, but it is currently unknown how pathological processes affect the expression of biological rhythms in the brain. Here, we use the unique opportunity of long-term, continuous intracranially recorded EEG from 38 patients (totalling 6338 hours) to delineate circadian and ultradian rhythms in different brain regions. We show that functional circadian and ultradian rhythms are diminished in pathological tissue, independent of regional variations. We further demonstrate that these diminished rhythms are persistent in time, regardless of load or occurrence of pathological events. These findings provide the first evidence that brain pathology is functionally associated with persistently diminished chronobiological rhythms in vivo in humans, independent of regional variations or pathological events. Future work interacting with, and restoring, these modulatory chronobiological rhythms may allow for novel therapies

A Naturally Narrow Positive Parity Theta^+

We present a consistent color-flavor-spin-orbital wave function for a positive parity Theta^+ that naturally explains the observed narrowness of the state. The wave function is totally symmetric in its flavor-spin part and totally antisymmetric in its color-orbital part. If flavor-spin interactions dominate, this wave function renders the positive parity Theta^+ lighter than its negative parity counterpart. We consider decays of the Theta^+ and compute the overlap of this state with the kinematically allowed final states. Our results are numerically small. We note that dynamical correlations between quarks are not necessary to obtain narrow pentaquark widths.Comment: 10 pages, 1 figure, Revtex4, two-column format, version to be published in Phys. Rev. D, includes numerical estimates of decay width

αEβ7 Integrin Identifies Subsets of Pro-Inflammatory Colonic CD4+ T Lymphocytes in Ulcerative Colitis.

Background and Aims The αEβ7 integrin is crucial for retention of T lymphocytes at mucosal surfaces through its interaction with E-cadherin. Pathogenic or protective functions of these cells during human intestinal inflammation, such as ulcerative colitis [UC], have not previously been defined, with understanding largely derived from animal model data. Defining this phenotype in human samples is important for understanding UC pathogenesis and is of translational importance for therapeutic targeting of αEβ7-E-cadherin interactions. Methods αEβ7+ and αEβ7- colonic T cell localization, inflammatory cytokine production and expression of regulatory T cell-associated markers were evaluated in cohorts of control subjects and patients with active UC by immunohistochemistry, flow cytometry and real-time PCR of FACS-purified cell populations. Results CD4+αEβ7+ T lymphocytes from both healthy controls and UC patients had lower expression of regulatory T cell-associated genes, including FOXP3, IL-10, CTLA-4 and ICOS in comparison with CD4+αEβ7- T lymphocytes. In UC, CD4+αEβ7+ lymphocytes expressed higher levels of IFNγ and TNFα in comparison with CD4+αEβ7- lymphocytes. Additionally the CD4+αEβ7+ subset was enriched for Th17 cells and the recently described Th17/Th1 subset co-expressing both IL-17A and IFNγ, both of which were found at higher frequencies in UC compared to control. Conclusion αEβ7 integrin expression on human colonic CD4+ T cells was associated with increased production of pro-inflammatory Th1, Th17 and Th17/Th1 cytokines, with reduced expression of regulatory T cell-associated markers. These data suggest colonic CD4+αEβ7+ T cells are pro-inflammatory and may play a role in UC pathobiology

Logical Development of the Cell Ontology

<p>Abstract</p> <p>Background</p> <p>The Cell Ontology (CL) is an ontology for the representation of <it>in vivo </it>cell types. As biological ontologies such as the CL grow in complexity, they become increasingly difficult to use and maintain. By making the information in the ontology computable, we can use automated reasoners to detect errors and assist with classification. Here we report on the generation of computable definitions for the hematopoietic cell types in the CL.</p> <p>Results</p> <p>Computable definitions for over 340 CL classes have been created using a genus-differentia approach. These define cell types according to multiple axes of classification such as the protein complexes found on the surface of a cell type, the biological processes participated in by a cell type, or the phenotypic characteristics associated with a cell type. We employed automated reasoners to verify the ontology and to reveal mistakes in manual curation. The implementation of this process exposed areas in the ontology where new cell type classes were needed to accommodate species-specific expression of cellular markers. Our use of reasoners also inferred new relationships within the CL, and between the CL and the contributing ontologies. This restructured ontology can be used to identify immune cells by flow cytometry, supports sophisticated biological queries involving cells, and helps generate new hypotheses about cell function based on similarities to other cell types.</p> <p>Conclusion</p> <p>Use of computable definitions enhances the development of the CL and supports the interoperability of OBO ontologies.</p