Keep Me Around: Intron Retention Detection and Analysis

We present a tool, keep me around (kma), a suite of python scripts and an R package that finds retained introns in RNA-Seq experiments and incorporates biological replicates to reduce the number of false positives when detecting retention events. kma uses the results of existing quantification tools that probabilistically assign multi-mapping reads, thus interfacing easily with transcript quantification pipelines. The data is represented in a convenient, database style format that allows for easy aggregation across introns, genes, samples, and conditions to allow for further exploratory analysis

Core Blighty? How Journalists Define Themselves Through Metaphor

Journalism has long relied on certain core metaphors in order to express its claims to social and political usefulness. The deployment of metaphors to describe a practice that in contrast asserts its truth-telling and plain prose style is in itself interesting. Since metaphor acts as a powerful indicator of presuppositions it can be used to reify complex public discourses, reducing them to common-sense thinking. This paper will explore what metaphors have been used in association with journalism in the pages of the British Journalism Review since the closure of the News of the World. This publication was launched in 1989 in response to a previous crisis in public and professional confidence in journalism and has since then provided an intriguing insider dialogue on developments within the area. Do metaphorical articulations of the current role and image of journalism demonstrate an awareness among journalists of changes in its values or do they rather tend to reinforce more traditional attitudes to a practice under threat? Post-Leveson what can the patterning of such figurative language across articles by a wide range of prominent journalists in the UK tell us about the values and aspirations of journalists in a time when journalism is under intense scrutiny

The splicing regulatory element, UGCAUG, is phylogenetically and spatially conserved in introns that flank tissue-specific alternative exons

Previous studies have identified UGCAUG as an intron splicing enhancer that is frequently located adjacent to tissue-specific alternative exons in the human genome. Here, we show that UGCAUG is phylogenetically and spatially conserved in introns that flank brain-enriched alternative exons from fish to man. Analysis of sequence from the mouse, rat, dog, chicken and pufferfish genomes revealed a strongly statistically significant association of UGCAUG with the proximal intron region downstream of brain-enriched alternative exons. The number, position and sequence context of intronic UGCAUG elements were highly conserved among mammals and in chicken, but more divergent in fish. Control datasets, including constitutive exons and non-tissue-specific alternative exons, exhibited a much lower incidence of closely linked UGCAUG elements. We propose that the high sequence specificity of the UGCAUG element, and its unique association with tissue-specific alternative exons, mark it as a critical component of splicing switch mechanism(s) designed to activate a limited repertoire of splicing events in cell type-specific patterns. We further speculate that highly conserved UGCAUG-binding protein(s) related to the recently described Fox-1 splicing factor play a critical role in mediating this specificity

Smooth transitions from Schwarzschild vacuum to de Sitter space

We provide an infinity of spacetimes which contain part of both the Schwarzschild vacuum and de Sitter space. The transition, which occurs below the Schwarzschild event horizon, involves only boundary surfaces (no surface layers). An explicit example is given in which the weak and strong energy conditions are satisfied everywhere (except in the de Sitter section) and the dominant energy condition is violated only in the vicinity of the boundary to the Schwarzschild section. The singularity is avoided by way of a change in topology in accord with a theorem due to Borde..Comment: revtex4, two figures. Final form to appear in Phys. Rev.

A dynamic intron retention program enriched in RNA processing genes regulates gene expression during terminal erythropoiesis

Differentiating erythroblasts execute a dynamic alternative splicing program shown here to include extensive and diverse intron retention (IR) events. Cluster analysis revealed hundreds of developmentally-dynamic introns that exhibit increased IR in mature erythroblasts, and are enriched in functions related to RNA processing such as SF3B1 spliceosomal factor. Distinct, developmentally-stable IR clusters are enriched in metal-ion binding functions and include mitoferrin genes SLC25A37 and SLC25A28 that are critical for iron homeostasis. Some IR transcripts are abundant, e.g. comprising ∼50% of highly-expressed SLC25A37 and SF3B1 transcripts in late erythroblasts, and thereby limiting functional mRNA levels. IR transcripts tested were predominantly nuclear-localized. Splice site strength correlated with IR among stable but not dynamic intron clusters, indicating distinct regulation of dynamically-increased IR in late erythroblasts. Retained introns were preferentially associated with alternative exons with premature termination codons (PTCs). High IR was observed in disease-causing genes including SF3B1 and the RNA binding protein FUS. Comparative studies demonstrated that the intron retention program in erythroblasts shares features with other tissues but ultimately is unique to erythropoiesis. We conclude that IR is a multi-dimensional set of processes that post-transcriptionally regulate diverse gene groups during normal erythropoiesis, misregulation of which could be responsible for human disease

Guide to Common Parasites of Food Fish Species in the Northwest Territories and Nunavut

Global Water Futures supported by the Canada First Research Excellence FundNon-Peer ReviewedPrepared by N. Zabel & Dr. H. Swanson, Wilfrid Laurier University, and reviewed by Dr. G. Conboy (DVM, PhD, DACVM), Atlantic Veterinary College, University of Prince Edward Island. Preparation of this guide was supported by Northern Water Futures (Global Water Futures; Canada First Research Excellence Fund). Reviews, photographs, and expert guidance was received as in-kind support from several individuals, and we gratefully acknowledge these important contributions. Funding for printing of guides distributed within Northwest Territories was provided by Government of Northwest Territories

Different Transport Pathways of Individual Precursor Proteins in Mitochondria

Transport of mitochondrial precursor proteins into mitochondria of Neurospora crassa was studied in a cellfree reconstituted system. Precursors were synthesized in a reticulocyte lysate programmed with Neurospora mRNA and transported into isolated mitochondria in the absence of protein synthesis. Uptake of the following precursors was investigated: apocytochrome c, ADP/ATP carrier and subunit 9 of the oligomycin-sensitive ATPase. Addition of high concentrations of unlabelled chemically prepared apocytochrome c (1–10 μM) inhibited the appearance in the mitochondrial of labelled cytochrome c synthesized in vitro because the unlabelled protein dilutes the labelled one and because the translocation system has a limited capacity [apparent V is 1–3 pmol × min−1× (mg mitochondrial protein)−1]. Concentrations of added apocytochrome c exceeding the concentrations of precursor proteins synthesized in vitro by a factor of about 104 did not inhibit the transfer of ADP/ATP carrier or ATPase subunit 9 into mitochondria. Carbonylcyanide m-chlorophenylhydrazone, an uncoupler of oxidative phosphorylation, inhibited transfer in vitro of ADP/ATP carrier and of ATPase subunit 9, but not of cytochrome c. These findings suggest that cytochrome c and the other two proteins have different import pathways into mitochondria. It can be inferred from the data presented that different 'receptors' on the mitochondrial surface mediate the specific recognition of precursor proteins by mitochondria as a first step in the transport process

Novel 4, 8-benzobisthiazole copolymers and their field-effect transistor and photovoltaic applications

A series of copolymers containing the benzo[1,2-d:4,5-d′]bis(thiazole) (BBT) unit has been designed and synthesised with bisthienyl-diketopyrrolopyrrole (DPP), dithienopyrrole (DTP), benzothiadiazole (BT), benzodithiophene (BDT) or 4,4′-dialkoxybithiazole (BTz) comonomers. The resulting polymers possess a conjugation pathway that is orthogonal to the more usual substitution pathway through the 2,6-positions of the BBT unit, facilitating intramolecular non-covalent interactions between strategically placed heteroatoms of neighbouring monomer units. Such interactions enable a control over the degree of planarity through altering their number and strength, in turn allowing for tuning of the band gap. The resulting 4,8-BBT materials gave enhanced mobility in p-type organic field-effect transistors of up to 2.16 × 10−2 cm2 V−1 s−1 for pDPP2ThBBT and good solar cell performance of up to 4.45% power conversion efficiency for pBT2ThBBT

Transport of Proteins into Mitochondria

The mitochondrial ADP/ATP carrier is an integral transmembrane protein of the inner membrane. It is synthesized on cytoplasmic ribosomes. Kinetic data suggested that this protein is transferred into mitochondria in a posttranslational manner. The following results provide further evidence for such a mechanism and provide information on its details. 1. In homologous and heterologous translation systems the newly synthesized ADP/ATP carrier protein is present in the postribosomal supernatant. 2. Analysis by density gradient centrifugation and gel filtration shows, that the ADP/ATP carrier molecules in the postribosomal fraction are present as soluble complexes with apparent molecular weights of about 120000 and 500000 or larger. The carrier binds detergents such as Triton X-100 and deoxycholate forming mixed micelles with molecular weights of about 200000–400000. 3. Incubation of a postribosomal supernatant of a reticulocyte lysate containing newly synthesized ADP/ATP carrier with mitochondria isolated from Neurospora spheroplasts results in efficient transfer of the carrier into mitochondria. About 20–30% of the transferred carrier are resistant to proteinase in whole mitochondria. The authentic mature protein is also largely resistant to proteinase in whole mitochondria and sensitive after lysis of mitochondria with detergent. Integrity of mitochondria is a prerequisite for translocation into proteinase resistant position. 4. The transfer in vitro into a proteinase-resistant form is inhibited by the uncoupler carbonyl-cyanide m-chlorophenylhydrazone but not the proteinase-sensitive binding. These observations suggest that the posttranslational transfer of ADP/ATP carrier occurs via the cytosolic space through a soluble oligomeric precursor form. This precursor is taken up by intact mitochondria into an integral position in the membrane. These findings are considered to be of general importance for the intracellular transfer of insoluble membrane proteins. They support the view that such proteins can exist in a water-soluble form its precursors and upon integration into the membrane undergo a conformational change. Uptake into the membrane may involve the cleavage of an additional sequence in some proteins, but this appears not to be a prerequisite as demonstrated by the ADP/ATP carrier protein