Scintillation in the Circinus Galaxy water megamasers

We present observations of the 22 GHz water vapor megamasers in the Circinus galaxy made with the Tidbinbilla 70m telescope. These observations confirm the rapid variability seen earlier by Greenhill et al (1997). We show that this rapid variability can be explained by interstellar scintillation, based on what is now known of the interstellar scintillation seen in a significant number of flat spectrum AGN. The observed variability cannot be fully described by a simple model of either weak or diffractive scintillation.Comment: 10 pages, 5 figures. AJ accepte

Psychotherapy mediated by remote communication technologies: a meta-analytic review

Reproduced with permission of the publisher. © 2008 Bee et al; licensee BioMed Central Ltd. The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-244X/8/60. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background Access to psychotherapy is limited by psychopathology (e.g. agoraphobia), physical disability, occupational or social constraints and/or residency in under-served areas. For these populations, interventions delivered via remote communication technologies (e.g. telephone, internet) may be more appropriate. However, there are concerns that such delivery may influence the therapeutic relationship and thus reduce therapy effectiveness. This review aimed to determine the clinical effectiveness of remotely communicated, therapist-delivered psychotherapy. Methods Systematic review (including electronic database searching and correspondence with authors) of randomised trials of individual remote psychotherapy. Electronic databases searched included MEDLINE (1966–2006), PsycInfo (1967–2006), EMBASE (1980–2006) and CINAHL databases (1982–2006). The Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDAN-CTR). All searches were conducted to include studies with a publication date to July 2006. Results Thirteen studies were identified, ten assessing psychotherapy by telephone, two by internet and one by videoconference. Pooled effect sizes for remote therapy versus control conditions were 0.44 for depression (95%CI 0.29 to 0.59, 7 comparisons, n = 726) and 1.15 for anxiety-related disorders (95%CI 0.81 to 1.49, 3 comparisons, n = 168). There were few comparisons of remote versus face-to-face psychotherapy. Conclusion Remote therapy has the potential to overcome some of the barriers to conventional psychological therapy services. Telephone-based interventions are a particularly popular research focus and as a means of therapeutic communication may confer specific advantages in terms of their widespread availability and ease of operation. However, the available evidence is limited in quantity and quality. More rigorous trials are required to confirm these preliminary estimates of effectiveness. Future research priorities should include overcoming the methodological shortcomings of published work by conducting large-scale trials that incorporate both clinical outcome and more process-orientated measures

Bcl-XL Inhibits Membrane Permeabilization by Competing with Bax

Although Bcl-XL and Bax are structurally similar, activated Bax forms large oligomers that permeabilize the outer mitochondrial membrane, thereby committing cells to apoptosis, whereas Bcl-XL inhibits this process. Two different models of Bcl-XL function have been proposed. In one, Bcl-XL binds to an activator, thereby preventing Bax activation. In the other, Bcl-XL binds directly to activated Bax. It has been difficult to sort out which interaction is important in cells, as all three proteins are present simultaneously. We examined the mechanism of Bax activation by tBid and its inhibition by Bcl-XL using full-length recombinant proteins and measuring permeabilization of liposomes and mitochondria in vitro. Our results demonstrate that Bcl-XL and Bax are functionally similar. Neither protein bound to membranes alone. However, the addition of tBid recruited molar excesses of either protein to membranes, indicating that tBid activates both pro- and antiapoptotic members of the Bcl-2 family. Bcl-XL competes with Bax for the activation of soluble, monomeric Bax through interaction with membranes, tBid, or t-Bid-activated Bax, thereby inhibiting Bax binding to membranes, oligomerization, and membrane permeabilization. Experiments in which individual interactions were abolished by mutagenesis indicate that both Bcl-XL–tBid and Bcl-XL–Bax binding contribute to the antiapoptotic function of Bcl-XL. By out-competing Bax for the interactions leading to membrane permeabilization, Bcl-XL ties up both tBid and Bax in nonproductive interactions and inhibits Bax binding to membranes. We propose that because Bcl-XL does not oligomerize it functions like a dominant-negative Bax in the membrane permeabilization process

propr: An R-package for identifying proportionally abundant features using compositional data analysis

In the life sciences, many assays measure only the relative abundances of components in each sample. Such data, called compositional data, require special treatment to avoid misleading conclusions. Awareness of the need for caution in analyzing compositional data is growing, including the understanding that correlation is not appropriate for relative data. Recently, researchers have proposed proportionality as a valid alternative to correlation for calculating pairwise association in relative data. Although the question of how to best measure proportionality remains open, we present here a computationally efficient R package that implements three measures of proportionality. In an effort to advance the understanding and application of proportionality analysis, we review the mathematics behind proportionality, demonstrate its application to genomic data, and discuss some ongoing challenges in the analysis of relative abundance data

The stealth episome: suppression of gene expression on the excised genomic island PPHGI-1 from Pseudomonas syringae pv. phaseolicola

Pseudomonas syringae pv. phaseolicola is the causative agent of halo blight in the common bean, Phaseolus vulgaris. P. syringae pv. phaseolicola race 4 strain 1302A contains the avirulence gene avrPphB (syn. hopAR1), which resides on PPHGI-1, a 106 kb genomic island. Loss of PPHGI-1 from P. syringae pv. phaseolicola 1302A following exposure to the hypersensitive resistance response (HR) leads to the evolution of strains with altered virulence. Here we have used fluorescent protein reporter systems to gain insight into the mobility of PPHGI-1. Confocal imaging of dual-labelled P. syringae pv. phaseolicola 1302A strain, F532 (dsRFP in chromosome and eGFP in PPHGI-1), revealed loss of PPHGI-1::eGFP encoded fluorescence during plant infection and when grown in vitro on extracted leaf apoplastic fluids. Fluorescence-activated cell sorting (FACS) of fluorescent and non-fluorescent PPHGI-1::eGFP F532 populations showed that cells lost fluorescence not only when the GI was deleted, but also when it had excised and was present as a circular episome. In addition to reduced expression of eGFP, quantitative PCR on sub-populations separated by FACS showed that transcription of other genes on PPHGI-1 (avrPphB and xerC) was also greatly reduced in F532 cells harbouring the excised PPHGI-1::eGFP episome. Our results show how virulence determinants located on mobile pathogenicity islands may be hidden from detection by host surveillance systems through the suppression of gene expression in the episomal state

Structural and ligand binding analyses of the periplasmic sensor domain of RsbU in Chlamydia trachomatis support a role in TCA cycle regulation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154297/1/mmi14401-sup-0001-Supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154297/2/mmi14401_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154297/3/mmi14401.pd

Titration-based screening for evaluation of natural product extracts: identification of an aspulvinone family of luciferase inhibitors

The chemical diversity of nature has tremendous potential for discovery of new molecular probes and medicinal agents. However, sensitivity of HTS assays to interfering components of crude extracts derived from plants, macro- and microorganisms has curtailed their use in lead discovery efforts. Here we describe a process for leveraging the concentration-response curves (CRCs) obtained from quantitative HTS to improve the initial selection of “actives” from a library of partially fractionated natural product extracts derived from marine actinomycetes and fungi. By using pharmacological activity, the first-pass CRC paradigm aims to improve the probability that labor-intensive subsequent steps of re-culturing, extraction and bioassay-guided isolation of active component(s) target the most promising strains and growth conditions. We illustrate how this process identified a family of fungal metabolites as potent inhibitors of firefly luciferase, subsequently resolved in molecular detail by x-ray crystallography

Motivated proteins: a web application for studying small three-dimensional protein motifs

<b>BACKGROUND:</b> Small loop-shaped motifs are common constituents of the three-dimensional structure of proteins. Typically they comprise between three and seven amino acid residues, and are defined by a combination of dihedral angles and hydrogen bonding partners. The most abundant of these are alphabeta-motifs, asx-motifs, asx-turns, beta-bulges, beta-bulge loops, beta-turns, nests, niches, Schellmann loops, ST-motifs, ST-staples and ST-turns.We have constructed a database of such motifs from a range of high-quality protein structures and built a web application as a visual interface to this. <b>DESCRIPTION:</b> The web application, Motivated Proteins, provides access to these 12 motifs (with 48 sub-categories) in a database of over 400 representative proteins. Queries can be made for specific categories or sub-categories of motif, motifs in the vicinity of ligands, motifs which include part of an enzyme active site, overlapping motifs, or motifs which include a particular amino acid sequence. Individual proteins can be specified, or, where appropriate, motifs for all proteins listed. The results of queries are presented in textual form as an (X)HTML table, and may be saved as parsable plain text or XML. Motifs can be viewed and manipulated either individually or in the context of the protein in the Jmol applet structural viewer. Cartoons of the motifs imposed on a linear representation of protein secondary structure are also provided. Summary information for the motifs is available, as are histograms of amino acid distribution, and graphs of dihedral angles at individual positions in the motifs. <b>CONCLUSION:</b> Motivated Proteins is a publicly and freely accessible web application that enables protein scientists to study small three-dimensional motifs without requiring knowledge of either Structured Query Language or the underlying database schem

Calibration procedures and first data set of Southern Ocean chlorophyll a profiles collected by elephant seals equipped with a newly developed CTD-fluorescence tags

In-situ observation of the marine environment has traditionally relied on ship-based platforms. The obvious consequence is that physical and biogeochemical properties have been dramatically undersampled, especially in the remote Southern Ocean (SO). The difficulty in obtaining in situ data represents the major limitations to our understanding, and interpretation of the coupling between physical forcing and the biogeochemical response. Southern elephant seals (Mirounga leonina) equipped with a new generation of oceanographic sensors can measure ocean structure in regions and seasons rarely observed with traditional oceanographic platforms. Over the last few years, seals have allowed for a considerable increase in temperature and salinity profiles from the SO. However we were still lacking information on the spatio-temporal variation of phytoplankton concentration. This information is critical to assess how the biological productivity of the SO, with direct consequences on the amount of CO2 "fixed" by the biological pump, will respond to global warming. In this research program, we use an innovative sampling fluorescence approach to quantify phytoplankton concentration at sea. For the first time, a low energy consumption fluorometer was added to Argos CTD-SRDL tags, and these novel instruments were deployed on 27 southern elephant seals between 25 December 2007 and the 4 February 2011. As many as 3388 fluorescence profiles associated with temperature and salinity measurements were thereby collected from a vast sector of the Southern Indian Ocean. This paper address the calibration issue of the fluorometer before being deployed on elephant seals and present the first results obtained for the Indian Sector of the Southern Ocean.This in situ system is implemented in synergy with satellite ocean colour radiometry. Satellite-derived data is limited to the surface layer and is restricted over the SO by extensive cloud cover. However, with the addition of these new tags, we're able to assess the 3 dimension distribution of phytoplankton concentration by foraging southern elephant seals. This approach reveals that for the Indian sector of the SO, the surface chlorophyll a (chl a) concentrations provided by MODIS were underestimated by a factor of the order of 2–3 compared to in situ measurements. The scientific outcomes of this program include an improved understanding of both the present state and variability in ocean biology, and the accompanying biogeochemistry, as well as the delivery of real-time and open-access data to scientists

The designability of protein switches by chemical rescue of structure: mechanisms of inactivation and reactivation

This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Journal of the American Chemical Society, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/ja407644b.The ability to selectively activate function of particular proteins via pharmacological agents is a longstanding goal in chemical biology. Recently, we reported an approach for designing a de novo allosteric effector site directly into the catalytic domain of an enzyme. This approach is distinct from traditional chemical rescue of enzymes in that it relies on disruption and restoration of structure, rather than active site chemistry, as a means to achieve modulate function. However, rationally identifying analogous de novo binding sites in other enzymes represents a key challenge for extending this approach to introduce allosteric control into other enzymes. Here we show that mutation sites leading to protein inactivation via tryptophan-to-glycine substitution and allowing (partial) reactivation by the subsequent addition of indole are remarkably frequent. Through a suite of methods including a cell-based reporter assay, computational structure prediction and energetic analysis, fluorescence studies, enzymology, pulse proteolysis, x-ray crystallography and hydrogen-deuterium mass spectrometry we find that these switchable proteins are most commonly modulated indirectly, through control of protein stability. Addition of indole in these cases rescues activity not by reverting a discrete conformational change, as we had observed in the sole previously reported example, but rather rescues activity by restoring protein stability. This important finding will dramatically impact the design of future switches and sensors built by this approach, since evaluating stability differences associated with cavity-forming mutations is a far more tractable task than predicting allosteric conformational changes. By analogy to natural signaling systems, the insights from this study further raise the exciting prospect of modulating stability to design optimal recognition properties into future de novo switches and sensors built through chemical rescue of structure