Receptor antagonism/agonism can be uncoupled from pharmacoperone activity

Pharmacoperones rescue misrouted mutants of the vasopressin receptor type 2 (V2R) and enable them to traffic to the correct biological locus where they function. Previously, a library of nearly 645,000 structures was interrogated with a high throughput screen; pharmacoperones were identified for V2R mutants with a view toward correcting the underlying mutational defects in nephrogenic diabetes insipidus. In the present study, an orthologous assay was used to evaluate hits from the earlier study. We found no consistent relation between antagonism or agonism and pharmacoperone activity. Active pharmacoperones were identified which had minimal antagonistic activity. This increases the therapeutic reach of these drugs, since virtually all pharmacoperone drugs reported to date were selected from peptidomimetic antagonists. Such mixed-activity drugs have a complex pharmacology limiting their therapeutic utility and requiring their removal prior to stimulation of the receptor with agonist

Nonpolitical Images Evoke Neural Predictors of Political Ideology

Political ideologies summarize dimensions of life that define how a person organizes their public and private behavior, including their attitudes associated with sex, family, education, and personal autonomy [1, 2]. Despite the abstract nature of such sensibilities, fundamental features of political ideology have been found to be deeply connected to basic biological mechanisms [3–7] that may serve to defend against environmental challenges like contamination and physical threat [8–12]. These results invite the provocative claim that neural responses to nonpolitical stimuli (like contaminated food or physical threats) should be highly predictive of abstract political opinions (like attitudes toward gun control and abortion) [13]. We applied a machinelearning method to fMRI data to test the hypotheses that brain responses to emotionally evocative images predict individual scores on a standard political ideology assay. Disgusting images, especially those related to animalreminder disgust (e.g., mutilated body), generate neural responses that are highly predictive of political orientation even though these neural predictors do not agree with participants’ conscious rating of the stimuli. Images from other affective categories do not support such predictions. Remarkably, brain responses to a single disgusting stimulus were sufficient to make accurate predictions about an individual subject’s political ideology. These results provide strong support for the idea that fundamental neural processing differences that emerge under the challenge of emotionally evocative stimuli may serve to structure political beliefs in ways formerly unappreciated

3' tag digital gene expression profiling of human brain and universal reference RNA using Illumina Genome Analyzer

<p>Abstract</p> <p>Background</p> <p>Massive parallel sequencing has the potential to replace microarrays as the method for transcriptome profiling. Currently there are two protocols: full-length RNA sequencing (RNA-SEQ) and 3'-tag digital gene expression (DGE). In this preliminary effort, we evaluated the 3' DGE approach using two reference RNA samples from the MicroArray Quality Control Consortium (MAQC).</p> <p>Results</p> <p>Using Brain RNA sample from multiple runs, we demonstrated that the transcript profiles from 3' DGE were highly reproducible between technical and biological replicates from libraries constructed by the same lab and even by different labs, and between two generations of Illumina's Genome Analyzers. Approximately 65% of all sequence reads mapped to mitochondrial genes, ribosomal RNAs, and canonical transcripts. The expression profiles of brain RNA and universal human reference RNA were compared which demonstrated that DGE was also highly quantitative with excellent correlation of differential expression with quantitative real-time PCR. Furthermore, one lane of 3' DGE sequencing, using the current sequencing chemistry and image processing software, had wider dynamic range for transcriptome profiling and was able to detect lower expressed genes which are normally below the detection threshold of microarrays.</p> <p>Conclusion</p> <p>3' tag DGE profiling with massive parallel sequencing achieved high sensitivity and reproducibility for transcriptome profiling. Although it lacks the ability of detecting alternative splicing events compared to RNA-SEQ, it is much more affordable and clearly out-performed microarrays (Affymetrix) in detecting lower abundant transcripts.</p

The effect of solvent choice on the gelation and final hydrogel properties of Fmoc–diphenylalanine

Gels can be formed by dissolving Fmoc–diphenylalanine (Fmoc–PhePhe or FmocFF) in an organic solvent and adding water. We show here that the choice and amount of organic solvent allows the rheological properties of the gel to be tuned. The differences in properties arise from the microstructure of the fibre network formed. The organic solvent can then be removed post-gelation, without significant changes in the rheological properties. Gels formed using acetone are meta-stable and crystals of FmocFF suitable for X-ray diffraction can be collected from this gel

The HST/ACS Coma Cluster Survey. II. Data Description and Source Catalogs

The Coma cluster was the target of a HST-ACS Treasury program designed for deep imaging in the F475W and F814W passbands. Although our survey was interrupted by the ACS instrument failure in 2007, the partially completed survey still covers ~50% of the core high-density region in Coma. Observations were performed for 25 fields that extend over a wide range of cluster-centric radii (~1.75 Mpc) with a total coverage area of 274 arcmin^2. The majority of the fields are located near the core region of Coma (19/25 pointings) with six additional fields in the south-west region of the cluster. In this paper we present reprocessed images and SExtractor source catalogs for our survey fields, including a detailed description of the methodology used for object detection and photometry, the subtraction of bright galaxies to measure faint underlying objects, and the use of simulations to assess the photometric accuracy and completeness of our catalogs. We also use simulations to perform aperture corrections for the SExtractor Kron magnitudes based only on the measured source flux and half-light radius. We have performed photometry for ~73,000 unique objects; one-half of our detections are brighter than the 10-sigma point-source detection limit at F814W=25.8 mag (AB). The slight majority of objects (60%) are unresolved or only marginally resolved by ACS. We estimate that Coma members are 5-10% of all source detections, which consist of a large population of unresolved objects (primarily GCs but also UCDs) and a wide variety of extended galaxies from a cD galaxy to dwarf LSB galaxies. The red sequence of Coma member galaxies has a constant slope and dispersion across 9 magnitudes (-21<M_F814W<-13). The initial data release for the HST-ACS Coma Treasury program was made available to the public in 2008 August. The images and catalogs described in this study relate to our second data release.Comment: Accepted for publication in ApJS. A high-resolution version is available at http://archdev.stsci.edu/pub/hlsp/coma/release2/PaperII.pd

The HST/ACS Coma Cluster Survey. II. Data Description and Source Catalogs

The Coma cluster, Abell 1656, was the target of a HST-ACS Treasury program designed for deep imaging in the F475W and F814W passbands. Although our survey was interrupted by the ACS instrument failure in early 2007, the partially-completed survey still covers approximately 50% of the core high density region in Coma. Observations were performed for twenty-five fields with a total coverage area of 274 aremin(sup 2), and extend over a wide range of cluster-centric radii (approximately 1.75 Mpe or 1 deg). The majority of the fields are located near the core region of Coma (19/25 pointings) with six additional fields in the south-west region of the cluster. In this paper we present SEXTRACTOR source catalogs generated from the processed images, including a detailed description of the methodology used for object detection and photometry, the subtraction of bright galaxies to measure faint underlying objects, and the use of simulations to assess the photometric accuracy and completeness of our catalogs. We also use simulations to perform aperture corrections for the SEXTRACTOR Kron magnitudes based only on the measured source flux and its half-light radius. We have performed photometry for 76,000 objects that consist of roughly equal numbers of extended galaxies and unresolved objects. Approximately two-thirds of all detections are brighter than F814W=26.5 mag (AB), which corresponds to the 10sigma, point-source detection limit. We estimate that Coma members are 5-10% of the source detections, including a large population of compact objects (primarily GCs, but also cEs and UCDs), and a wide variety of extended galaxies from cD galaxies to dwarf low surface brightness galaxies. The initial data release for the HST-ACS Coma Treasury program was made available to the public in August 2008. The images and catalogs described in this study relate to our second data release

The Radio Luminosity Function and Galaxy Evolution in the Coma Cluster

We investigate the radio luminosity function (RLF) and radio source population for two fields within the Coma cluster of galaxies. Our VLA data reach down to log(L) = 20.23 W/Hz for Coma, and we associate 249 sources with optical counterparts from the SDSS. Comprehensive optical spectroscopy identifies 38 of these as members of the Coma cluster, evenly split between AGN and star-forming galaxies (SFG). The radio-detected SFG are the dominant population only for ~21 < log(L) < ~22 W/Hz, an interesting result given that star formation dominates field RLFs for log(L) < ~23. The majority of the radio-detected SFGs have characteristics of starbursts, including high specific star formation rates and optical spectra with strong emission lines. In conjunction with prior studies on post-starburst galaxies within the Coma cluster, this is consistent with a picture in which late-type galaxies entering Coma undergo a starburst prior to a rapid cessation of star formation. Optically bright elliptical galaxies (Mr <= -20.5) make the largest contribution to the radio luminosity function at both the high (log(L) >~ 22.48 W/Hz) and low (log(L) <~ 21 W/Hz) ends. Through a stacking analysis of these optically-bright ellipticals we find that they continue to harbor radio sources down to log(L) = 19.48. However, contrary to published results for the Virgo cluster we find no evidence for the existence of a population of optically faint (Mr ~ -14) dwarf ellipticals hosting strong radio AGN.Comment: 45 pages with 13 figures, accepted for publication in A

The Vehicle, Spring 1993

1993 Commemorative Edition: Celebrating 35 Years Table of Contents The Vehicle Editors\u27 Lineagepage 5 Milestonespage 6 THE SIXTIES Coverspage 7 Editors\u27 Notespage 8 Sureness is Never - excerptDon Shepardsonpage 9 SophisticationBenjamin Polkpage 10 A SonnetMignon Stricklandpage 11 The Twenty-Third ChannelBen Polkpage 11 Opposite AttractionsC.E.M. (Christine McColl)page 12 John F. KennedyJoel E. Hendrickspage 13 The Girl on the White PonyLarry Gatespage 14 The TimesW.D.M. (William Moser)page 16 Home ThoughtsJane Careypage 17 1966Roger Zulaufpage 18 Nagging ThoughtJanet Andrewspage 18 THE SEVENTIES Coverspage 19 Editors\u27 Notespage 20 RevolutionsSteve Siegelpage 21 UntitledKristine Kirkhampage 23 The Arithmetic ProblemJanice Forbuspage 23 Willie Seeverson Threw a Worm at MeMary Pipekpage 24 a love poem (by approximation)Ted Baldwinpage 25 Night and Summer in Two WorldsBarry Smithpage 26 Story of a Teenage PickleTerry Louis Schultzpage 27 Danny Lonely, Danny WildDevin Brownpage 28 Always TomorrowMary McDanielpage 29 THE EIGHTIES Coverspage 31 Having ChildrenDevon Flesorpage 33 What is Unnatural Is Sometimes MagicAngelique Jenningspage 34 If My Father Were A Writer, He Would Still BuildAngelique Jenningspage 35 Photo AlbumPatrick Peterspage 36 Poet Born in Pearl HarborAngelique Jenningspage 37 The History of High School BasketballPatrick Peterspage 38 Banana BreadGail Bowerpage 39 Cover LetterBob Zordanipage 40 Home MoviesBob Zordanipage 41 MigrationPatrick Peterspage 42 THE NINETIES Ba, Ba, Black SheepVictoria Bennettpage 45 Daily LessonsJennifer Moropage 49 Folding My OwnLaurie Ann Malispage 51 About the Authorspage 53 Editors\u27 Notespage 56https://thekeep.eiu.edu/vehicle/1062/thumbnail.jp