MBNL1 binds GC motifs embedded in pyrimidines to regulate alternative splicing

Muscleblind-like 1 (MBNL1) regulates alternative splicing and is a key player in the disease mechanism of myotonic dystrophy (DM). In DM, MBNL1 becomes sequestered to expanded CUG/CCUG repeat RNAs resulting in splicing defects, which lead to disease symptoms. In order to understand MBNL1’s role in both the disease mechanism of DM and alternative splicing regulation, we sought to identify its RNA-binding motif. A doped SELEX was performed on a known MBNL1-binding site. After five rounds of SELEX, MBNL1 selected pyrimidine-rich RNAs containing YGCY motifs. Insertion of multiple YGCY motifs into a normally MBNL1-independent splicing reporter was sufficient to promote regulation by MBNL1. MBNL1 was also shown to regulate the splicing of exon 22 in the ATP2A1 pre-mRNA, an exon mis-spliced in DM, via YGCY motifs. A search for YGCY motifs in 24 pre-mRNA transcripts that are mis-spliced in DM1 patients revealed an interesting pattern relative to the regulated exon. The intronic regions upstream of exons that are excluded in normal tissues relative to DM1, are enriched in YGCY motifs. Meanwhile, the intronic regions downstream of exons that are included in normal tissues relative to DM1, are enriched in YGCY motifs

Role of the K1K_1 meson in K0K^0 photoproduction off the deuteron

Neutral kaon photoproduction off the nucleon and deuteron has been reinvestigated by utilizing the new experimental data on both targets. An isobar model for elementary operator and impulse approximation for the reaction on the deuteron have been used. The available free parameters in the elementary model have been extracted from both elementary and deuteron data. In contrast to the elementary reaction, fitting the deuteron data requires an inclusion of weighting factor. The result indicates that the angular distribution of the elementary $K^0\Lambda$ process does not show backward peaking behavior.Comment: 4 pages, 4 figures, prepared for the Fifth Asia-Pacific Conference on Few-Body Problems in Physics 2011 (APFB2011), Seoul, Korea, August 22-26, 201

Chiral SU(3) Dynamics with Coupled Channels: Inclusion of P-Wave Multipoles

We extend our recent non-perturbative chiral SU(3) coupled channel approach to pion- and photon-induced $\eta$- and $K$-meson production off protons by including all strong and electromagnetic p-wave multipoles. We identify the p-wave amplitudes of the next-to-leading order SU(3) chiral meson-baryon Lagrangian with a coupled channel potential which is iterated to infinite orders in a separable Lippmann-Schwinger equation. Our approach to $\eta$- and $K$-photoproduction introduces no additional free parameters. By adjusting a few finite range parameters and the unknown parameters in the Lagrangian, we are able to simultaneously describe a very large amount of low-energy data. These include the total and differential cross sections of the $\pi$-induced reactions $\pi^- p \to \eta n, K^0 \Lambda, K^0 \Sigma^0, K^+ \Sigma^-$ and $\pi^+ p \to K^+ \Sigma^+$ as well as those of photoproduction $\gamma p \to \eta p, K^+\Lambda, K^+ \Sigma^0, K^0 \Sigma^+$. The polarization observables measured in $\eta$- and $K$-photoproduction are particularly sensitive to interference terms between the s- and p-wave multipoles. The total cross section data are remarkably well reproduced in all channels. There remain, however, some open questions concerning details of angular distributions and polarization observables.Comment: 20 pages, 5 figures, accepted for publication in Nucl. Phys.

Quark model predictions for K∗K^* photoproduction on the proton

The photoproduction of $K^*$ vector mesons is investigated in a quark model with an effective Lagrangian. Including both baryon resonance excitations and {\it t}-channel exchanges, observables for the reactions $\gamma p\to K^{*0}\Sigma^+$ and $\gamma p\to K^{*+}\Sigma^0$ are predicted, using the SU(3)-flavor-blind assumption of non-perturbative QCD.Comment: Revtex, 3 eps figures, revised version accepted by PRC Rapid Comm

K0-Sigma+ Photoproduction with SAPHIR

Preliminary results of the analysis of the reaction p(gamma,K0)Sigma+ are presented. We show the first measurement of the differential cross section and much improved data for the total cross section than previous data. The data are compared with model predictions from different isobar and quark models that give a good description of p(gamma,K+)Lambda and p(gamma,K+)Sigma0 data in the same energy range. Results of ChPT describe the data adequately at threshold while isobar models that include hadronic form factors reproduce the data at intermediate energies.Comment: 4 pages, Latex2e, 4 postscript figures. Talk given at the International Conference on Hypernuclear and Strange Particle Physics (HYP97), Brookhaven National Laboratory, USA, October 13-18, 1997. To be published in Nucl. Phys. A. Revised version due to changes in experimental dat

Drosophila muscleblind Codes for Proteins with One and Two Tandem Zinc Finger Motifs

Muscleblind-like proteins, Muscleblind (Mbl) in Drosophila and MBNL1-3 in vertebrates, are regulators of alternative splicing. Human MBNL1 is a key factor in the etiology of myotonic dystrophy (DM), a muscle wasting disease caused by the occurrence of toxic RNA molecules containing CUG/CCUG repeats. MBNL1 binds to these RNAs and is sequestered in nuclear foci preventing it from exerting its normal function, which ultimately leads to mis-spliced mRNAs, a major cause of the disease. Muscleblind-proteins bind to RNAs via N-terminal zinc fingers of the Cys3-His type. These zinc fingers are arranged in one (invertebrates) or two (vertebrates) tandem zinc finger (TZF) motifs with both fingers targeting GC steps in the RNA molecule. Here I show that mbl genes in Drosophila and in other insects also encode proteins with two TZF motifs, highly similar to vertebrate MBNL proteins. In Drosophila the different protein isoforms have overlapping but possibly divergent functions in vivo, evident by their unequal capacities to rescue the splicing defects observed in mbl mutant embryos. In addition, using whole transcriptome analysis, I identified several new splicing targets for Mbl in Drosophila embryos. Two of these novel targets, kkv (krotzkopf-verkehrt, coding for Chitin Synthase 1) and cora (coracle, coding for the Drosophila homolog of Protein 4.1), are not muscle-specific but expressed mainly in epidermal cells, indicating a function for mbl not only in muscles and the nervous system

Vector meson production and nucleon resonance analysis in a coupled-channel approach for energies m_N < sqrt(s) < 2 GeV II: photon-induced results

We present a nucleon resonance analysis by simultaneously considering all pion- and photon-induced experimental data on the final states gamma N, pi N, 2 pi N, eta N, K Lambda, K Sigma, and omega N for energies from the nucleon mass up to sqrt(s) = 2 GeV. In this analysis we find strong evidence for the resonances P_{31}(1750), P_{13}(1900), P_{33}(1920), and D_{13}(1950). The omega N production mechanism is dominated by large P_{11}(1710) and P_{13}(1900) contributions. In this second part we present the results on the photoproduction reactions and the electromagnetic properties of the resonances. The inclusion of all important final states up to sqrt(s) = 2 GeV allows for estimates on the importance of the individual states for the GDH sum rule.Comment: 41 pages, 26 figures, discussion extended, typos corrected, references updated, to appear in Phys. Rev.

Jet production in charged current deep inelastic e⁺p scatteringat HERA

The production rates and substructure of jets have been studied in charged current deep inelastic e⁺p scattering for Q² > 200 GeV² with the ZEUS detector at HERA using an integrated luminosity of 110.5 pb⁻¹. Inclusive jet cross sections are presented for jets with transverse energies E_{T}^{jet} > 5 GeV. Measurements of the mean subjet multiplicity, 〈n_{sbj}〉, of the inclusive jet sample are presented. Predictions based on parton-shower Monte Carlo models and next-to-leading-order QCD calculations are compared to the measurements. The value of α_{s} (M_{z}), determined from 〈n_{sbj}〉 at y_{cut} = 10⁻² for jets with 25 < E_{T}^{jet} < 119 GeV, is α_{s} (M_{z}) = 0.1202 ± 0.0052 (stat.)_{-0.0019}^{+0.0060} (syst.)_{-0.0053}^{+0.0065} (th.). The mean subjet multiplicity as a function of Q² is found to be consistent with that measured in NC DIS

Multijet production in neutral current deep inelastic scattering at HERA and determination of α_{s}

Multijet production rates in neutral current deep inelastic scattering have been measured in the range of exchanged boson virtualities 10 5 GeV and –1 < η_{LAB}^{jet} < 2.5. Next-to-leading-order QCD calculations describe the data well. The value of the strong coupling constant α_{s} (M_{z}), determined from the ratio of the trijet to dijet cross sections, is α_{s} (M_{z}) = 0.1179 ± 0.0013 (stat.)_{-0.0046}^{+0.0028}(exp.)_{-0.0046}^{+0.0028}(th.)

Beauty photoproduction measured using decays into muons in dijet events in ep collisions at s\sqrt{s}=318 GeV

The photoproduction of beauty quarks in events with two jets and a muon has been measured with the ZEUS detector at HERA using an integrated luminosity of 110 pb$^{- 1}$. The fraction of jets containing b quarks was extracted from the transverse momentum distribution of the muon relative to the closest jet. Differential cross sections for beauty production as a function of the transverse momentum and pseudorapidity of the muon, of the associated jet and of $x_{\gamma}^{jets}$, the fraction of the photon's momentum participating in the hard process, are compared with MC models and QCD predictions made at next-to-leading order. The latter give a good description of the data.Comment: 32 pages, 6 tables, 7 figures Table 6 and Figure 7 revised September 200