55 research outputs found
The splicing landscape is globally reprogrammed during male meiosis
Get PDFMeiosis requires conserved transcriptional changes, but it is not known whether there is a corresponding set of RNA splicing switches. Here, we used RNAseq of mouse testis to identify changes associated with the progression from mitotic spermatogonia to meiotic spermatocytes. We identified ∼150 splicing switches, most of which affect conserved protein-coding exons. The expression of many key splicing regulators changed in the course of meiosis, including downregulation of polypyrimidine tract binding protein (PTBP1) and heterogeneous nuclear RNP A1, and upregulation of nPTB, Tra2β, muscleblind, CELF proteins, Sam68 and T-STAR. The sequences near the regulated exons were significantly enriched in target sites for PTB, Tra2β and STAR proteins. Reporter minigene experiments investigating representative exons in transfected cells showed that PTB binding sites were critical for splicing of a cassette exon in the Ralgps2 mRNA and a shift in alternative 5' splice site usage in the Bptf mRNA. We speculate that nPTB might functionally replace PTBP1 during meiosis for some target exons, with changes in the expression of other splicing factors helping to establish meiotic splicing patterns. Our data suggest that there are substantial changes in the determinants and patterns of alternative splicing in the mitotic-to-meiotic transition of the germ cell cycle
Required experimental accuracy to select between supersymmetrical models
Get PDFWe will present a method to decidea priori whether various supersymmetrical scenarios can be distinguished based on sparticle mass data alone. For each model, a scan over all free SUSY breaking parameters reveals the extent of that model’s physically allowed region of sparticle-mass-space. Based on the geometrical configuration of these regions in mass-space, it is possible to obtain an estimate of the required accuracy of future sparticle mass measurements to distinguish between the models. We will illustrate this algorithm with an example. This talk is based on work done in collaboration with B C Allanach (LAPTH, Annecy) and F Quevedo (DAMTP, Cambridge)
Identification of evolutionarily conserved exons as regulated targets for the splicing activator Tra2β in development
Get PDFAlternative splicing amplifies the information content of the genome, creating multiple mRNA isoforms from single genes. The evolutionarily conserved splicing activator Tra2β (Sfrs10) is essential for mouse embryogenesis and implicated in spermatogenesis. Here we find that Tra2β is up-regulated as the mitotic stem cell containing population of male germ cells differentiate into meiotic and post-meiotic cells. Using CLIP coupled to deep sequencing, we found that Tra2β binds a high frequency of exons and identified specific G/A rich motifs as frequent targets. Significantly, for the first time we have analysed the splicing effect of Sfrs10 depletion in vivo by generating a conditional neuronal-specific Sfrs10 knock-out mouse (Sfrs10 fl/fl; Nestin-Cre tg/+). This mouse has defects in brain development and allowed correlation of genuine physiologically Tra2β regulated exons. These belonged to a novel class which were longer than average size and importantly needed multiple cooperative Tra2β binding sites for efficient splicing activation, thus explaining the observed splicing defects in the knockout mice. Regulated exons included a cassette exon which produces a meiotic isoform of the Nasp histone chaperone that helps monitor DNA double-strand breaks. We also found a previously uncharacterised poison exon identifying a new pathway of feedback control between vertebrate Tra2 proteins. Both Nasp-T and the Tra2a poison exon are evolutionarily conserved, suggesting they might control fundamental developmental processes. Tra2β protein isoforms lacking the RRM were able to activate specific target exons indicating an additional functional role as a splicing co-activator. Significantly the N-terminal RS1 domain conserved between flies and humans was essential for the splicing activator function of Tra2β. Versions of Tra2β lacking this N-terminal RS1 domain potently repressed the same target exons activated by full-length Tra2β protein. © 2011 Grellscheid et al
MERISTEM-DEFECTIVE regulates the balance between stemness and differentiation in the root meristem through RNA splicing control
Get PDFPlants respond to environmental stresses through controlled stem cell maintenance and meristem activity. One level of gene regulation is RNA alternative splicing. However, the mechanistic link between stress, meristem function and RNA splicing is poorly understood. The MERISTEM-DEFECTIVE (MDF) Arabidopsis gene encodes an SR-related family protein, required for meristem function and leaf vascularization, and is the likely orthologue of the human SART1 and yeast Snu66 splicing factors. MDF is required for the correct splicing and expression of key transcripts associated with root meristem function. We identified RSZ33 and ACC1, both known to regulate cell patterning, as splicing targets required for MDF function in the meristem. MDF expression is modulated by osmotic and cold stress, associated with differential splicing and specific isoform accumulation and shuttling between nucleus and cytosol, and acts in part via a splicing target SR34. We propose a model in which MDF controls splicing in the root meristem to promote stemness and to repress stress response, cell differentiation and cell death pathways
Simulation of Tau Decays in the Herwig++ Event Generator
No full textWe describe the simulation of tau decays in the Herwig++ event generator, which includes sophisticated modelling of the hadronic currents and full treatment of spin correlation effects. The structure of the simulation makes it easy to add new models of tau decay,change the parameters of the existing models, and use the models from tau decay for the decay of other particles. The results are compared in detail with an existing simulation, and the benefits of the new structure are illustrated by considering the decay of the lightest chargino to the lightest neutralino in Anomaly-Mediated SUSY-Breaking models
Monte Carlo Simulations of Heavy Particles for the Large Hadron Collider
Get PDFAs the Large Hadron Collider has switched on at CERN in Geneva, accurate predictions for complex hadronic processes are essential for the validation of theory and therefore the success of the machine. After motivating the requirement for a Monte Carlo event generator, the principles and Physics behind such a generator are laid out.
Following this, the Monte Carlo tuning system Professor is used to give an assessment of the uncertainty from tuning Herwig++ and the results from this analysis used, along with a more accurate implementation of Higgs boson decays using the POWHEG method, to determine the error associated with searching for the Higgs boson with a jet substructure technique.
Then, modifications to the shower to take into account the top quark width are presented along with radiation patterns from top quark production processes for up to two external gluons. A general algorithm is outlined for systematically including these corrections.
Finally, as the LHC is ultimately a discovery machine, it is pertinent to provide Monte Carlo studies of new Physics. The colour sextet diquark model is looked at in the final chapter of this thesis, and the associated phenomenology studied
YODA
No full text<p>YODA -- Yet more Objects for Data Analysis -- is a lightweight C++ and Python package for weighted histogramming and reference data manipulation. It is particularly associated with the Rivet MC event analysis framework for High-Energy Physics, but has been written with general-purpose applications in mind.</p>
YODA
No full textYODA -- Yet more Objects for Data Analysis -- is a lightweight C++ and Python package for weighted histogramming and reference data manipulation. It is particularly associated with the Rivet MC event analysis framework for High-Energy Physics, but has been written with general-purpose applications in mind
YODA
No full text<p>YODA -- Yet more Objects for Data Analysis -- is a lightweight C++ and Python package for weighted histogramming and reference data manipulation. It is particularly associated with the Rivet MC event analysis framework for High-Energy Physics, but has been written with general-purpose applications in mind.</p>
Constraining new physics with collider measurements of Standard Model signatures
Get PDF: A new method providing general consistency constraints for Beyond-theStandard-Model
(BSM) theories, using measurements at particle colliders, is presented.
The method, ‘Constraints On New Theories Using Rivet’, Contur, exploits the fact that
particle-level differential measurements made in fiducial regions of phase-space have a high
degree of model-independence. These measurements can therefore be compared to BSM
physics implemented in Monte Carlo generators in a very generic way, allowing a wider
array of final states to be considered than is typically the case. The Contur approach
should be seen as complementary to the discovery potential of direct searches, being designed
to eliminate inconsistent BSM proposals in a context where many (but perhaps not
all) measurements are consistent with the Standard Model. We demonstrate, using a competitive
simplified dark matter model, the power of this approach. The Contur method
is highly scaleable to other models and future measurements
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