Six1 homeoprotein drives myofiber type IIA specialization in soleus muscle

International audienceAbstractBackgroundAdult skeletal muscles are composed of slow and fast myofiber subtypes which each express selective genes required for their specific contractile and metabolic activity. Six homeoproteins are transcription factors regulating muscle cell fate through activation of myogenic regulatory factors and driving fast-type gene expression during embryogenesis.ResultsWe show here that Six1 protein accumulates more robustly in the nuclei of adult fast-type muscles than in adult slow-type muscles, this specific enrichment takes place during perinatal growth. Deletion of Six1 in soleus impaired fast-type myofiber specialization during perinatal development, resulting in a slow phenotype and a complete lack of Myosin heavy chain 2A (MyHCIIA) expression. Global transcriptomic analysis of wild-type and Six1 mutant myofibers identified the gene networks controlled by Six1 in adult soleus muscle. This analysis showed that Six1 is required for the expression of numerous genes encoding fast-type sarcomeric proteins, glycolytic enzymes and controlling intracellular calcium homeostasis. Parvalbumin, a key player of calcium buffering, in particular, is a direct target of Six1 in the adult myofiber.ConclusionsThis analysis revealed that Six1 controls distinct aspects of adult muscle physiology in vivo, and acts as a main determinant of fast-fiber type acquisition and maintenance

Study of B−→DK−π+π−B^{-}\to DK^-\pi^+\pi^- and B−→Dπ−π+π−B^-\to D\pi^-\pi^+\pi^- decays and determination of the CKM angle γ\gamma

We report a study of the suppressed $B^-\to DK^-\pi^+\pi^-$ and favored $B^-\to D\pi^-\pi^+\pi^-$ decays, where the neutral $D$ meson is detected through its decays to the $K^{\mp}\pi^{\pm}$ and CP-even $K^+K^-$ and $\pi^+\pi^-$ final states. The measurement is carried out using a proton-proton collision data sample collected by the LHCb experiment, corresponding to an integrated luminosity of 3.0~fb$^{-1}$. We observe the first significant signals in the CP-even final states of the $D$ meson for both the suppressed $B^-\to DK^-\pi^+\pi^-$ and favored $B^-\to D\pi^-\pi^+\pi^-$ modes, as well as in the doubly Cabibbo-suppressed $D\to K^+\pi^-$ final state of the $B^-\to D\pi^-\pi^+\pi^-$ decay. Evidence for the ADS suppressed decay $B^{-}\to DK^-\pi^+\pi^-$, with $D\to K^+\pi^-$, is also presented. From the observed yields in the $B^-\to DK^-\pi^+\pi^-$, $B^-\to D\pi^-\pi^+\pi^-$ and their charge conjugate decay modes, we measure the value of the weak phase to be $\gamma=(74^{+20}_{-19})^{\rm o}$. This is one of the most precise single-measurement determinations of $\gamma$ to date.Comment: 22 pages, 9 figures; All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-020.htm

Measurement of the branching fraction ratio B(Bc+→ψ(2S)π+)/B(Bc+→J/ψπ+)\mathcal{B}(B_c^+ \rightarrow \psi(2S)\pi^+)/\mathcal{B}(B_c^+ \rightarrow J/\psi \pi^+)

Using $pp$ collision data collected by LHCb at center-of-mass energies $\sqrt{s}$ = 7 TeV and 8 TeV, corresponding to an integrated luminosity of 3 fb$^{-1}$, the ratio of the branching fraction of the $B_c^+ \rightarrow \psi(2S)\pi^+$ decay relative to that of the $B_c^+ \rightarrow J/\psi\pi^+$ decay is measured to be 0.268 $\pm$ 0.032 (stat) $\pm$ 0.007 (syst) $\pm$ 0.006 (BF). The first uncertainty is statistical, the second is systematic, and the third is due to the uncertainties on the branching fractions of the $J/\psi \rightarrow \mu^+\mu^-$ and $\psi(2S) \rightarrow \mu^+\mu^-$ decays. This measurement is consistent with the previous LHCb result, and the statistical uncertainty is halved.Comment: 17 pages including author list, 2 figure

Study of WW boson production in association with beauty and charm

The associated production of a $W$ boson with a jet originating from either a light parton or heavy-flavor quark is studied in the forward region using proton-proton collisions. The analysis uses data corresponding to integrated luminosities of 1.0 and $2.0\,{\rm fb}^{-1}$ collected with the LHCb detector at center-of-mass energies of 7 and 8 TeV, respectively. The $W$ bosons are reconstructed using the $W\to\mu\nu$ decay and muons with a transverse momentum, $p_{\rm T}$, larger than 20 GeV in the pseudorapidity range $2.0 20$ GeV and $2.2 < \eta < 4.2$. The sum of the muon and jet momenta must satisfy $p_{\rm T} > 20$ GeV. The fraction of $W+$jet events that originate from beauty and charm quarks is measured, along with the charge asymmetries of the $W\!+\!b$ and $W\!+\!c$ production cross-sections. The ratio of the $W+$jet to $Z+$jet production cross-sections is also measured using the $Z\to\mu\mu$ decay. All results are in agreement with Standard Model predictions

Amplitude analysis of B0→Dˉ0K+π−B^0 \rightarrow \bar{D}^0 K^+ \pi^- decays

The Dalitz plot distribution of $B^0 \rightarrow \bar{D}^0 K^+ \pi^-$ decays is studied using a data sample corresponding to $3.0\rm{fb}^{-1}$ of $pp$ collision data recorded by the LHCb experiment during 2011 and 2012. The data are described by an amplitude model that contains contributions from intermediate $K^*(892)^0$, $K^*(1410)^0$, $K^*_2(1430)^0$ and $D^*_2(2460)^-$ resonances. The model also contains components to describe broad structures, including the $K^*_0(1430)^0$ and $D^*_0(2400)^-$ resonances, in the $K\pi$ S-wave and the $D\pi$ S- and P-waves. The masses and widths of the $D^*_0(2400)^-$ and $D^*_2(2460)^-$ resonances are measured, as are the complex amplitudes and fit fractions for all components included in the amplitude model. The model obtained will be an integral part of a future determination of the angle $\gamma$ of the CKM quark mixing matrix using $B^0 \rightarrow D K^+ \pi^-$ decays.Comment: 33 pages, 12 figures; updated for publicatio

Measurement of the ratio of branching fractions B(B‾0→D∗+τ−ν‾τ)/B(B‾0→D∗+μ−ν‾μ)\mathcal{B}(\overline{B}^0 \to D^{*+}\tau^{-}\overline{\nu}_{\tau})/\mathcal{B}(\overline{B}^0 \to D^{*+}\mu^{-}\overline{\nu}_{\mu})

The branching fraction ratio $\mathcal{R}(D^{*}) \equiv \mathcal{B}(\overline{B}^0 \to D^{*+}\tau^{-}\overline{\nu}_{\tau})/\mathcal{B}(\overline{B}^0 \to D^{*+}\mu^{-}\overline{\nu}_{\mu})$ is measured using a sample of proton-proton collision data corresponding to 3.0\invfb of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode $\tau^{-} \to \mu^{-}\overline{\nu}_{\mu}\nu_{\tau}$. The semitauonic decay is sensitive to contributions from non-Standard-Model particles that preferentially couple to the third generation of fermions, in particular Higgs-like charged scalars. A multidimensional fit to kinematic distributions of the candidate $\overline{B}^0$ decays gives $\mathcal{R}(D^{*}) = 0.336 \pm 0.027(stat) \pm 0.030 (syst)$. This result, which is the first measurement of this quantity at a hadron collider, is $2.1$ standard deviations larger than the value expected from lepton universality in the Standard Model.Comment: 17 pages, 1 figure. v2 after referees' comment

Identification of new genetic susceptibility loci for breast cancer through consideration of gene-environment interactions

Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10(−07)), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m(2) (OR = 1.26, 95% CI 1.15–1.38) but not in women with a BMI of 30 kg/m(2) or higher (OR = 0.89, 95% CI 0.72–1.11, P for interaction = 3.2 × 10(−05)). Our findings confirm comparable power of the recent methods for detecting G × E interaction and the utility of using G × E interaction analyses to identify new susceptibility loci

Genetic modifiers of CHEK2*1100delC-associated breast cancer risk

Purpose: CHEK2*1100delC is a founder variant in European populations that confers a two-to threefold increased risk of breast cancer (BC). Epidemiologic and family studies have suggested that the risk associated with CHEK2*1100delC is modified by other genetic factors in a multiplicative fashion. We have investigated this empirically using data from the Breast Cancer Association Consortium (BCAC). Methods: Using genotype data from 39,139 (624 1100delC carriers) BC patients and 40,063 (224) healthy controls from 32 BCAC studies, we analyzed the combined risk effects of CHEK2*1100delC and 77 common variants in terms of a polygenic risk score (PRS) and pairwise interaction. Results: The PRS conferred odds ratios (OR) of 1.59 (95% CI: 1.212.09) per standard deviation for BC for CHEK2*1100delC carriers and 1.58 (1.55-1.62) for noncarriers. No evidence of deviation from the multiplicative model was found. The OR for the highest quintile of the PRS was 2.03 (0.86-4.78) for CHEK2*1100delC carriers, placing them in the high risk category according to UK NICE guidelines. The OR for the lowest quintile was 0.52 (0.16-1.74), indicating a lifetime risk close to the population average. Conclusion: Our results confirm the multiplicative nature of risk effects conferred by CHEK2*1100delC and the common susceptibility variants. Furthermore, the PRS could identify carriers at a high lifetime risk for clinical actions.Peer reviewe

First Observation of Top Quark Production in the Forward Region

Top quark production in the forward region in proton-proton collisions is observed for the first time. The $W\!+\!b$ final state with $W\to\mu\nu$ is reconstructed using muons with a transverse momentum, $p_{\rm T}$, larger than 25 GeV in the pseudorapidity range $2.0<\eta<4.5$. The $b$ jets are required to have $50 < p_{\rm T} < 100$ GeV and $2.2 < \eta < 4.2$, while the transverse component of the sum of the muon and $b$-jet momenta must satisfy $p_{\rm T} > 20$ GeV. The results are based on data corresponding to integrated luminosities of 1.0 and $2.0$ fb$^{-1}$ collected at center-of-mass energies of 7 and 8 TeV by LHCb. The inclusive top quark production cross-sections in the fiducial region are $\sigma({\rm top})[7\rm{TeV}] = 239\pm53({\rm stat})\pm33({\rm syst})\pm24({\rm theory})\,{\rm fb}$ and $\sigma({\rm top})[8\rm{TeV}] = 289\pm43({\rm stat})\pm40({\rm syst})\pm29({\rm theory})\,{\rm fb}$. These results, along with the observed differential yields and charge asymmetries, are in agreement with next-to-leading order Standard Model predictions