699 research outputs found
Using cellular fitness to map the structure and function of a major facilitator superfamily effluxer.
The major facilitator superfamily (MFS) effluxers are prominent mediators of antimicrobial resistance. The biochemical characterization of MFS proteins is hindered by their complex membrane environment that makes in vitro biochemical analysis challenging. Since the physicochemical properties of proteins drive the fitness of an organism, we posed the question of whether we could reverse that relationship and derive meaningful biochemical parameters for a single protein simply from fitness changes it confers under varying strengths of selection. Here, we present a physiological model that uses cellular fitness as a proxy to predict the biochemical properties of the MFS tetracycline efflux pump, TetB, and a family of single amino acid variants. We determined two lumped biochemical parameters roughly describing Km and Vmax for TetB and variants. Including in vivo protein levels into our model allowed for more specified prediction of pump parameters relating to substrate binding affinity and pumping efficiency for TetB and variants. We further demonstrated the general utility of our model by solely using fitness to assay a library of tet(B) variants and estimate their biochemical properties
Our Space: Being a Responsible Citizen of the Digital World
Our Space is a set of curricular materials designed to encourage high school students to reflect on the ethical dimensions of their participation in new media environments. Through role-playing activities and reflective exercises, students are asked to consider the ethical responsibilities of other people, and whether and how they behave ethically themselves online. These issues are raised in relation to five core themes that are highly relevant online: identity, privacy, authorship and ownership, credibility, and participation.Our Space was co-developed by The Good Play Project and Project New Media Literacies (established at MIT and now housed at University of Southern California's Annenberg School for Communications and Journalism). The Our Space collaboration grew out of a shared interest in fostering ethical thinking and conduct among young people when exercising new media skills
Kapsula
This experimental exhibition catalogue was created
in collaboration with Gallery 44 Centre for Contemporary Photograpy in Toronto, Canada to document their twenty-first annual exhibition of emergent photography, Proof. The Magazine would like to extend a special thanks to Noa Bronstein, Head of Exhibitions and Publications at Gallery 44, both for her contributions to the document itself and for making this special issue possible
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Individual Differences in Correspondence Bias: Measurement, Consequences, and Correction of Biased Interpersonal Attributions
Across consequential attributions of attitudes, ability, emotions, and morality, people make correspondent inferences. People infer stable personality characteristics from others’ behavior, even when that behavior is caused by situational factors. We examined the structure of correspondent inferences and report the development and validation of an instrument measuring individual differences in this correspondence bias (a Neglect of External Demands scale, or “NED”). The NED is internally consistent and distinct from scales and measures of intelligence, cognitive ability, cognitive reflection, general decision making ability, preference for control, and attributional style. Individual differences in correspondence bias predict blaming people for harmful accidents, believing coerced confessions, correcting for job and task difficulty when making performance evaluations and incentive-compatible personnel selections, and separating market and fund performance when making incentive-compatible investments. Fortunately, the tendency to commit correspondence bias can be reduced. Making situational information easier to process debiases those most prone to correspondence bias
Kapsula
This experimental exhibition catalogue was created
in collaboration with Gallery 44 Centre for Contemporary Photograpy in Toronto, Canada to document their twenty-first annual exhibition of emergent photography, Proof. The Magazine would like to extend a special thanks to Noa Bronstein, Head of Exhibitions and Publications at Gallery 44, both for her contributions to the document itself and for making this special issue possible
Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context
Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
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