Curating gene sets: challenges and opportunities for integrative analysis.

Genomic data interpretation often requires analyses that move from a gene-by-gene focus to a focus on sets of genes that are associated with biological phenomena such as molecular processes, phenotypes, diseases, drug interactions or environmental conditions. Unique challenges exist in the curation of gene sets beyond the challenges in curation of individual genes. Here we highlight a literature curation workflow whereby gene sets are curated from peer-reviewed published data into GeneWeaver (GW), a data repository and analysis platform. We describe the system features that allow for a flexible yet precise curation procedure. We illustrate the value of curation by gene sets through analysis of independently curated sets that relate to the integrated stress response, showing that sets curated from independent sources all share significant Jaccard similarity. A suite of reproducible analysis tools is provided in GW as services to carry out interactive functional investigation of user-submitted gene sets within the context of over 150 000 gene sets constructed from publicly available resources and published gene lists. A curation interface supports the ability of users to design and maintain curation workflows of gene sets, including assigning, reviewing and releasing gene sets within a curation project context

Magnetic Field Structure of the Large Magellanic Cloud from Faraday Rotation Measures of Diffuse Polarized Emission

We present a study of the magnetic field of the Large Magellanic Cloud (LMC), carried out using diffuse polarized synchrotron emission data at 1.4 GHz acquired at the Parkes Radio Telescope and the Australia Telescope Compact Array. The observed diffuse polarized emission is likely to originate above the LMC disk on the near side of the galaxy. Consistent negative rotation measures (RMs) derived from the diffuse emission indicate that the line-of-sight magnetic field in the LMC's near-side halo is directed coherently away from us. In combination with RMs of extragalactic sources that lie behind the galaxy, we show that the LMC's large scale magnetic field is likely to be of quadrupolar geometry, consistent with the prediction of dynamo theory. On smaller scales, we identify two brightly polarized filaments southeast of the LMC, associated with neutral hydrogen arms. The filaments' magnetic field potentially aligns with the direction towards the Small Magellanic Cloud. We suggest that tidal interactions between the Small and the Large Magellanic Clouds in the past 10^9 years is likely to have shaped the magnetic field in these filaments.Comment: 42 pages, 22 figures, 2 tables. Accepted for publication in ApJ. Electronic version of Table 2 is available via email from the first autho

AMI-LA radio continuum observations of Spitzer c2d small clouds and cores: Perseus region

We present deep radio continuum observations of the cores identified as deeply embedded young stellar objects in the Perseus molecular cloud by the Spitzer c2d programme at a wavelength of 1.8 cm with the Arcminute Microkelvin Imager Large Array (AMI-LA). We detect 72% of Class 0 objects from this sample and 31% of Class I objects. No starless cores are detected. We use the flux densities measured from these data to improve constraints on the correlations between radio luminosity and bolometric luminosity, infrared luminosity and, where measured, outflow force. We discuss the differing behaviour of these objects as a function of protostellar class and investigate the differences in radio emission as a function of core mass. Two of four possible very low luminosity objects (VeLLOs) are detected at 1.8 cm.Comment: 18 pages, 9 figures, accepted MNRA

The Clostridium difficile Cell Wall Protein CwpV is Antigenically Variable between Strains, but Exhibits Conserved Aggregation-Promoting Function

Clostridium difficile is the main cause of antibiotic-associated diarrhea, leading to significant morbidity and mortality and putting considerable economic pressure on healthcare systems. Current knowledge of the molecular basis of pathogenesis is limited primarily to the activities and regulation of two major toxins. In contrast, little is known of mechanisms used in colonization of the enteric system. C. difficile expresses a proteinaceous array on its cell surface known as the S-layer, consisting primarily of the major S-layer protein SlpA and a family of SlpA homologues, the cell wall protein (CWP) family. CwpV is the largest member of this family and is expressed in a phase variable manner. Here we show CwpV promotes C. difficile aggregation, mediated by the C-terminal repetitive domain. This domain varies markedly between strains; five distinct repeat types were identified and were shown to be antigenically distinct. Other aspects of CwpV are, however, conserved. All CwpV types are expressed in a phase variable manner. Using targeted gene knock-out, we show that a single site-specific recombinase RecV is required for CwpV phase variation. CwpV is post-translationally cleaved at a conserved site leading to formation of a complex of cleavage products. The highly conserved N-terminus anchors the CwpV complex to the cell surface. Therefore CwpV function, regulation and processing are highly conserved across C. difficile strains, whilst the functional domain exists in at least five antigenically distinct forms. This hints at a complex evolutionary history for CwpV

Overview of mathematical approaches used to model bacterial chemotaxis II: bacterial populations

We review the application of mathematical modeling to understanding the behavior of populations of chemotactic bacteria. The application of continuum mathematical models, in particular generalized Keller–Segel models, is discussed along with attempts to incorporate the microscale (individual) behavior on the macroscale, modeling the interaction between different species of bacteria, the interaction of bacteria with their environment, and methods used to obtain experimentally verified parameter values. We allude briefly to the role of modeling pattern formation in understanding collective behavior within bacterial populations. Various aspects of each model are discussed and areas for possible future research are postulated

A submillimeter exponential disk in M~51: evidence for an extended cold dust disk

A 850 micron map of the interacting spiral galaxy M51 shows well-defined spiral arms, closely resembling the structures seen in CO and HI emission. However, most of the 850 micron emission originates in an underlying exponential disk, a component that has not been observed before in a face-on galaxy at these wavelengths. The scale-length of this disk is 5.45 kpc, which is somewhat larger than the scale-length of the stellar disk, but somewhat smaller than that of atomic hydrogen. Its profile can not be explained solely by a radial disk temperature gradient but requires the underlying dust to have an exponential distribution as well. This reinforces the view that the submm emission from spiral galaxy disks traces total hydrogen column density, i.e.the sum of H2 and HI. A canonical gas-to-dust ratio of 100+/-26 is obtained for kappa(850)=1.2 g**-1 cm**2, where kappa(850) is the dust opacity at 850 micron.Comment: accepted by A&A, 8 page

Reporting animal research:Explanation and elaboration for the ARRIVE guidelines 2.0

Improving the reproducibility of biomedical research is a major challenge. Transparent and accurate reporting is vital to this process; it allows readers to assess the reliability of the findings and repeat or build upon the work of other researchers. The ARRIVE guidelines (Animal Research: Reporting In Vivo Experiments) were developed in 2010 to help authors and journals identify the minimum information necessary to report in publications describing in vivo experiments. Despite widespread endorsement by the scientific community, the impact of ARRIVE on the transparency of reporting in animal research publications has been limited. We have revised the ARRIVE guidelines to update them and facilitate their use in practice. The revised guidelines are published alongside this paper. This explanation and elaboration document was developed as part of the revision. It provides further information about each of the 21 items in ARRIVE 2.0, including the rationale and supporting evidence for their inclusion in the guidelines, elaboration of details to report, and examples of good reporting from the published literature. This document also covers advice and best practice in the design and conduct of animal studies to support researchers in improving standards from the start of the experimental design process through to publication