Probabilistic Clustering of Sequences: Inferring new bacterial regulons by comparative genomics

Genome wide comparisons between enteric bacteria yield large sets of conserved putative regulatory sites on a gene by gene basis that need to be clustered into regulons. Using the assumption that regulatory sites can be represented as samples from weight matrices we derive a unique probability distribution for assignments of sites into clusters. Our algorithm, 'PROCSE' (probabilistic clustering of sequences), uses Monte-Carlo sampling of this distribution to partition and align thousands of short DNA sequences into clusters. The algorithm internally determines the number of clusters from the data, and assigns significance to the resulting clusters. We place theoretical limits on the ability of any algorithm to correctly cluster sequences drawn from weight matrices (WMs) when these WMs are unknown. Our analysis suggests that the set of all putative sites for a single genome (e.g. E. coli) is largely inadequate for clustering. When sites from different genomes are combined and all the homologous sites from the various species are used as a block, clustering becomes feasible. We predict 50-100 new regulons as well as many new members of existing regulons, potentially doubling the number of known regulatory sites in E. coli.Comment: 27 pages including 9 figures and 3 table

The effects of female sex hormones (birth control contraceptive) on measures of endothelial function

Background: Endothelial function has been shown to be influenced by many variables, including, but not limited to body composition, disease state, dietary fat intake, medication, and sex hormones, in particular estrogen. Specifically in women, changes in the functioning level of endothelial cells vary in response to changes in estrogen levels in the body. Purpose: The purpose of this study was to investigate the effects of hormonal birth control contraceptives on endothelial function, or more specifically, on flow-mediated dilatation (FMD). Method: 61 female participants between the ages of 18 and 28 (21.54 ± 2.03) with BMI ranging from 17.47 to 35.03 (23.04 ± 3.37) were recruited for this study from Texas Christian University by word of mouth and flier. Upon enrollment into the study, participants completed a medical questionnaire and signed a University approved informed consent. Based on self-report, the group was divided into those using birth control contraceptives (BC, n = 31) and those not using contraceptives (NC, n = 30). Endothelial function was assessed via FMD of the brachial artery using an Acuson, Aspin Advance color Doppler ultrasound unit with a L10 linear array transducer. Briefly, with the subjects in a supine position, the diameter of the brachial artery was measured in longitudinal section image using the caliper system in the Acuson ultrasound unit. The brachial artery was then occluded for 5 min with a blood pressure cuff inflated to 50 mmHg above systolic blood pressure. For 5 min following the occlusion, an image of the blood vessel diameter was obtained every 30 sec. Results: The average pre-occlusion and peak FMD responses for the groups were 0.295 ± 0.034 and 0.351 ± 0.034 cm, and 0.308 ± 0.039 and 0.373 ± 0.044 cm for the BC and NC groups, respectively. This corresponded to an average FMD percent change of 19.27 ± 9.27 and 21.52 ± 7.02 for the BC and NC groups, respectively. No significant difference was found between the two groups for either absolute or percent change responses. Conclusion: Birth control medications do not influence endothelial function assessed via flow-mediated dilatation

Playing the game: service users' management of risk status in a UK medium secure forensic mental health service

In this article we examine how forensic mental health service users actively attempt to manage their risk status through playing the game of containing frustration and demonstrating compliance. The article draws on an observational study (2006 to 2009) which explored the practices of risk assessment and management within one inner city forensic mental health medium secure service in the UK. We used a grounded theory approach to explore service users and providers experiences of risk assessment and management. We interviewed forensic mental health service users and providers. We also collected data using participant and non-participant observation. Since access to forensic mental health services is tightly controlled, there are participant observation studies undertaken in these settings. We found that service users attempted to understand the system of assessment and sought to affect and reduce their risk status by engaging in overt, compliant behaviours. We argue that in doing so service users are active agents in the process of risk management. However, we indicate that there are adverse effects of this approach to risk management as the risk assessment process is subverted by the restriction of the flow of information, and service users are left with frustrations that they must contain and manage

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table

SCOPmap: Automated assignment of protein structures to evolutionary superfamilies

BACKGROUND: Inference of remote homology between proteins is very challenging and remains a prerogative of an expert. Thus a significant drawback to the use of evolutionary-based protein structure classifications is the difficulty in assigning new proteins to unique positions in the classification scheme with automatic methods. To address this issue, we have developed an algorithm to map protein domains to an existing structural classification scheme and have applied it to the SCOP database. RESULTS: The general strategy employed by this algorithm is to combine the results of several existing sequence and structure comparison tools applied to a query protein of known structure in order to find the homologs already classified in SCOP database and thus determine classification assignments. The algorithm is able to map domains within newly solved structures to the appropriate SCOP superfamily level with ~95% accuracy. Examples of correctly mapped remote homologs are discussed. The algorithm is also capable of identifying potential evolutionary relationships not specified in the SCOP database, thus helping to make it better. The strategy of the mapping algorithm is not limited to SCOP and can be applied to any other evolutionary-based classification scheme as well. SCOPmap is available for download. CONCLUSION: The SCOPmap program is useful for assigning domains in newly solved structures to appropriate superfamilies and for identifying evolutionary links between different superfamilies

<i>Gaia</i> Data Release 1. Summary of the astrometric, photometric, and survey properties

Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7. Aims. A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release. Methods. The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue. Results. Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the HIPPARCOS and Tycho-2 catalogues – a realisation of the Tycho-Gaia Astrometric Solution (TGAS) – and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of ∼3000 Cepheid and RR-Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr−1 for the proper motions. A systematic component of ∼0.3 mas should be added to the parallax uncertainties. For the subset of ∼94 000 HIPPARCOS stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr−1. For the secondary astrometric data set, the typical uncertainty of the positions is ∼10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to ∼0.03 mag over the magnitude range 5 to 20.7. Conclusions. Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data

Radical SAM enzyme QueE defines a new minimal core fold and metal-dependent mechanism

7-carboxy-7-deazaguanine synthase (QueE) catalyzes a key S-adenosyl-L-methionine (AdoMet)- and Mg[superscript 2+]-dependent radical-mediated ring contraction step, which is common to the biosynthetic pathways of all deazapurine-containing compounds. QueE is a member of the AdoMet radical superfamily, which employs the 5′-deoxyadenosyl radical from reductive cleavage of AdoMet to initiate chemistry. To provide a mechanistic rationale for this elaborate transformation, we present the crystal structure of a QueE along with structures of pre- and post-turnover states. We find that substrate binds perpendicular to the [4Fe-4S]-bound AdoMet, exposing its C6 hydrogen atom for abstraction and generating the binding site for Mg[superscript 2+], which coordinates directly to the substrate. The Burkholderia multivorans structure reported here varies from all other previously characterized members of the AdoMet radical superfamily in that it contains a hypermodified ([β [subscript 6] over α [subscript 3]]) protein core and an expanded cluster-binding motif, CX[subscript 14]CX[subscript 2]C.United States. Dept. of Energy. Office of Biological and Environmental ResearchUnited States. Dept. of Energy. Office of Basic Energy SciencesNational Center for Research Resources (U.S.) (P41RR012408)National Institute of General Medical Sciences (U.S.) (P41GM103473)National Center for Research Resources (U.S.) (5P41RR015301-10)National Institute of General Medical Sciences (U.S.) (8 P41 GM 103403-10)United States. Dept. of Energy (Contract DE-AC02-06CH11357