Functional improvement of dystrophic muscle by repression of utrophin: let-7c interaction

Duchenne muscular dystrophy (DMD) is a fatal genetic disease caused by an absence of the 427kD muscle-specific dystrophin isoform. Utrophin is the autosomal homolog of dystrophin and when overexpressed, can compensate for the absence of dystrophin and rescue the dystrophic phenotype of the mdx mouse model of DMD. Utrophin is subject to miRNA mediated repression by several miRNAs including let-7c. Inhibition of utrophin: let-7c interaction is predicted to 'repress the repression' and increase utrophin expression. We developed and tested the ability of an oligonucleotide, composed of 2'-O-methyl modified bases on a phosphorothioate backbone, to anneal to the utrophin 3'UTR and prevent let-7c miRNA binding, thereby upregulating utrophin expression and improving the dystrophic phenotype in vivo. Suppression of utrophin: let-7c interaction using bi-weekly intraperitoneal injections of let7 site blocking oligonucleotides (SBOs) for 1 month in the mdx mouse model for DMD, led to increased utrophin expression along with improved muscle histology, decreased fibrosis and increased specific force. The functional improvement of dystrophic muscle achieved using let7-SBOs suggests a novel utrophin upregulation-based therapeutic strategy for DMD

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Search for leptophobic Z ' bosons decaying into four-lepton final states in proton-proton collisions at root s=8 TeV

Peer reviewe

Search for black holes and other new phenomena in high-multiplicity final states in proton-proton collisions at root s=13 TeV

Peer reviewe

Measurements of differential production cross sections for a Z boson in association with jets in pp collisions at root s=8 TeV

Peer reviewe

Search for high-mass diphoton resonances in proton-proton collisions at 13 TeV and combination with 8 TeV search

Peer reviewe

Search for heavy resonances decaying into a vector boson and a Higgs boson in final states with charged leptons, neutrinos, and b quarks

Peer reviewe

Search for neutral resonances decaying into a Z boson and a pair of b jets or τ leptons

A search is performed for a new resonance decaying into a lighter resonance and a Z boson. Two channels are studied, targeting the decay of the lighter resonance into either a pair of oppositely charged τ leptons or a bb‾ pair. The Z boson is identified via its decays to electrons or muons. The search exploits data collected by the CMS experiment at a centre-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 19.8 fb −1 . No significant deviations are observed from the standard model expectation and limits are set on production cross sections and parameters of two-Higgs-doublet models

Search for a low-mass pseudoscalar Higgs boson produced in association with a bb⁻ pair in pp collisions at √s=8 TeV

A search is reported for a light pseudoscalar Higgs boson decaying to a pair of tau leptons, produced in association with a b (b) over bar pair, in the context of two-Higgs-doublet models. The results are based on pp collision data at a centre-of-mass energy of 8 TeV collected by the CMS experiment at the LHC and corresponding to an integrated luminosity of 19.7 fb(-1). Pseudoscalar boson masses between 25 and 80 GeV are probed. No evidence for a pseudoscalar boson is found and upper limits are set on the product of cross section and branching fraction to tau pairs between 7 and 39 pb at the 95% confidence level. This excludes pseudoscalar A bosons with masses between 25 and 80 GeV, with SM-like Higgs boson negative couplings to down-type fermions, produced in association with bb pairs, in Type II, two-Higgs-doublet models. (C) 2016 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommonnorg/licensesiby/4.01)