Adhesion between cells, diffusion of growth factors, and elasticity of the AER produce the paddle shape of the chick limb

This paper has been withdrawnComment: This paper has been withdraw

A Complete Expression Profile of Matrix-Degrading Metalloproteinases in Dupuytren’s Disease

Dupuytren’s disease (DD) is a common fibrotic condition of the palmar fascia, leading to deposition of collagen-rich cords and finger contractions. The metzincin superfamily contains key enzymes in the turnover of collagen and other extracellular matrix macromolecules. A number of broad-spectrum matrix metalloproteinase inhibitors, used in cancer clinical trials, caused side effects of DD-like contractures. We tested the hypothesis that changes in the expression of specific metalloproteinases underlie or contribute to the fibrosis and contracture seen in DD. We collected tissue from patients with DD and used normal palmar fascia as a control. We profiled the expression of the entire matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinases (TIMP), and a disintegrin and metalloproteinase domain with thrombospondin motif (ADAMTS) gene families in these tissues using real-time reverse-transcription polymerase chain reaction. A number of metalloproteinases and inhibitors are regulated in DD. The expression of 3 key collagenases, MMP1, MMP13, and MMP14 is increased significantly in the DD nodule, as is the expression of the collagen biosynthetic enzyme ADAMTS14. The expression of MMP7, an enzyme with broad substrate specificity, is increased in the DD nodule and remains equally expressed in the DD cord. TIMP1 expression is increased significantly in DD nodule compared with normal palmar fascia. This study measured the expression of all MMP, ADAMTS, and TIMP genes in DD. Contraction and fibrosis may result from: (1) increased collagen biosynthesis mediated by increased ADAMTS-14; (2) an increased level of TIMP-1 blocking MMP-1– and MMP-13–mediated collagenolysis; and (3) contraction enabled by MMP-14–mediated pericellular collagenolysis (and potentially MMP-7), which may escape inhibition by TIMP-1. The complete expression profile will provide a knowledge-based approach to novel therapeutics targeting these genes

Atmospheric gamma-ray observation with the BETS detectorfor calibrating atmospheric neutrino flux calculations

We observed atmospheric gamma-rays around 10 GeV at balloon altitudes (15~25 km) and at a mountain (2770 m a.s.l). The observed results were compared with Monte Carlo calculations to find that an interaction model (Lund Fritiof1.6) used in an old neutrino flux calculation was not good enough for describing the observed values. In stead, we found that two other nuclear interaction models, Lund Fritiof7.02 and dpmjet3.03, gave much better agreement with the observations. Our data will serve for examining nuclear interaction models and for deriving a reliable absolute atmospheric neutrino flux in the GeV region.We observed atmospheric gamma-rays around 10 GeV at balloon altitudes (15~25 km) and at a mountain (2770 m a.s.l). The observed results were compared with Monte Carlo calculations to find that an interaction model (Lund Fritiof1.6) used in an old neutrino flux calculation was not good enough for describing the observed values. In stead, we found that two other nuclear interaction models, Lund Fritiof7.02 and dpmjet3.03, gave much better agreement with the observations. Our data will serve for examining nuclear interaction models and for deriving a reliable absolute atmospheric neutrino flux in the GeV region

A Novel Hypothesis for Thalidomide-Induced Limb Teratogenesis: Redox Misregulation of the NF-κB Pathway

Several hypotheses have been proposed to explain the mechanisms of thalidomide teratogenesis, although none adequately accounts for the observed malformations and explains the basis for species specificity. Recent observations that thalidomide increases the production of free radicals and elicits oxidative stress, coupled with new insights into the redox regulation of nuclear transcription factors, lead to the suggestion that thalidomide may act through redox misregulation of the limb outgrowth pathways. Oxidative stress, as marked by glutathione depletion/oxidation and a shift in intracellular redox potential toward the positive, occurs preferentially in limbs of thalidomide-sensitive rabbits, but not in resistant rats. DNA binding of nuclear factor κ-B (NF-κB), a redox-sensitive transcription factor and key regulator of limb outgrowth, was shown to be significantly attenuated in rabbit limb cells and could be restored following the addition of a free radical spin-trapping agent, phenyl N-tert-butyl nitrone. The inability of NF-κB to bind to its DNA promoter results in the failure of limb cells to express fibroblast growth factor (FGF)-10 and twist in the limb progress zone (PZ) mesenchyme, which in turn attenuates expression of FGF-8 in the apical ectodermal ridge (AER). Failure to establish an FGF-10/FGF-8 feedback loop between the PZ and AER results in the truncation of limb outgrowth. We hypothesize that species-selective alterations in redox microenvironment caused by free radical production from thalidomide results in attenuation of the NF-κB-mediated gene expression that is responsible for limb outgrowth.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63400/1/152308604771978291.pd

Risk Factors For Recurrent Stroke After Coronary Artery Bypass Grafting

<p>Abstract</p> <p>Objectives</p> <p>Preventing stroke after coronary artery bypass grafting (CABG) remains a therapeutic goal, due in part to the lack of identifiable risk factors. The aim of this study, accordingly, was to identify risk factors in CABG patients with a previous history of stroke.</p> <p>Methods</p> <p>Patients with a history of stroke who underwent CABG at Beijing An Zhen hospital from January 2007 to July 2010 were selected (n = 430), and divided into two groups according to the occurrence of postoperative stroke. Pre-operative and post-operative data were retrospectively collected and analyzed by univariate and multivariate logistic regression analyses.</p> <p>Results</p> <p>Thirty-two patients (7.4%) suffered post-operative stroke. Univariate analysis identified several statistically significant risk factors in the post-operative stroke group, including pre-surgical left ventricular ejection fractions (LVEF) ≤50%, on-pump surgery, post-operative atrial fibrillation (AF), and hypotension. Multivariable analysis identified 4 independent risk factors for recurrent stroke: unstable angina (odds ratio (OR) = 2.95, 95% CI: 1.05-8.28), LVEF ≤50% (OR = 2.77, 95% CI: 1.23-6.27), AF (OR = 4.69, 95% CI: 1.89-11.63), and hypotension (OR = 2.55, 95% CI: 1.07-6.04).</p> <p>Conclusion</p> <p>Unstable angina, LVEF ≤50%, post-operative AF, and post-operative hypotension are independent risk factors of recurrent stroke in CABG patients with a previous history of stroke.</p

Observation of B0->pi0pi0

We report the first observation of the decay B0->pi0pi0, using a 253/fb data sample collected at the Upsilon(4S) resonance with the Belle detector at the KEKB e+e- collider. The measured branching fraction is BF(B0->pi0pi0) = {2.32 +0.4-0.5(stat) +0.2-0.3(syst)} x 10^-6, with a significance of 5.8 standard deviations including systematic uncertainties. We also make the first measurement of the direct CP violating asymmetry in this mode.Comment: 6 pages, 2 figures, submitted to ICHEP04, Beijing and Physical Review Letters. v2: a possible pile-up background is checked and a systematic error for it is include

Engineering a family of synthetic splicing ribozymes

Controlling RNA splicing opens up possibilities for the synthetic biologist. The Tetrahymena ribozyme is a model group I self-splicing ribozyme that has been shown to be useful in synthetic circuits. To create additional splicing ribozymes that can function in synthetic circuits, we generated synthetic ribozyme variants by rationally mutating the Tetrahymena ribozyme. We present an alignment visualization for the ribozyme termed as structure information diagram that is similar to a sequence logo but with alignment data mapped on to secondary structure information. Using the alignment data and known biochemical information about the Tetrahymena ribozyme, we designed synthetic ribozymes with different primary sequences without altering the secondary structure. One synthetic ribozyme with 110 nt mutated retained 12% splicing efficiency in vivo. The results indicate that our biochemical understanding of the ribozyme is accurate enough to engineer a family of active splicing ribozymes with similar secondary structure but different primary sequences

Observation of Large CP Violation and Evidence for Direct CP Violation in B0-->pi+pi- Decays

We report the first observation of CP-violating asymmetries in B0 --> pi+pi- decays based on a 140 fb-1 data sample collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider. We reconstruct one neutral B meson as a B0 --> pi+pi- CP eigenstate and identify the flavor of the accompanying B meson from its decay products. We apply an unbinned maximum likelihood fit to the distribution of the time intervals between the two B meson decay points. The fit yields the CP-violating asymmetry amplitudes Apipi = +0.58+/-0.15(stat)+/-0.07(syst) and Spipi = -1.00+/-0.21(stat)+/-0.07(syst). We rule out the CP-conserving case, Apipi=Spipi=0, at a level of 5.2 standard deviations. We also find evidence for direct CP violation with a significance at or greater than 3.2 standard deviations for any Spipi value.Comment: 9 pages, 3 figure

Observation of the DsJ(2317) and DsJ(2457) in B decays

We report the first observation of the B --> Dbar DsJ(2317) and B --> Dbar DsJ(2457) decays based on 123.8 10^6 BBar events collected with the Belle detector at KEKB. We observe the DsJ(2317) decay to Ds pi0 and DsJ(2457) decay to the Ds* pi0 and Ds gamma final states. We also set 90% CL upper limits for the decays DsJ(2317) --> Ds* gamma, DsJ(2457) --> Ds* gamma, DsJ(2457) --> Ds pi0 and DsJ(2457) --> Ds pi+ pi-.Comment: 6 pages, 3 figures. A few minor corrections. Replaced by version accepted to publication in Phys. Rev. Let