Genome-Wide Studies Reveal that H3K4me3 Modification in Bivalent Genes Is Dynamically Regulated during the Pluripotent Cell Cycle and Stabilized upon Differentiation

Indexación: Web of Science; Scopus.Stem cell phenotypes are reflected by posttranslational histone modifications, and this chromatin-related memory must be mitotically inherited to maintain cell identity through proliferative expansion. In human embryonic stem cells (hESCs), bivalent genes with both activating (H3K4me3) and repressive (H3K27me3) histone modifications are essential to sustain pluripotency. Yet, the molecular mechanisms by which this epigenetic landscape is transferred to progeny cells remain to be established. By mapping genomic enrichment of H3K4me3/H3K27me3 in pure populations of hESCs in G2, mitotic, and G1 phases of the cell cycle, we found striking variations in the levels of H3K4me3 through the G2-M-G1 transition. Analysis of a representative set of bivalent genes revealed that chromatin modifiers involved in H3K4 methylation/demethylation are recruited to bivalent gene promoters in a cell cycle-dependent fashion. Interestingly, bivalent genes enriched with H3K4me3 exclusively during mitosis undergo the strongest upregulation after induction of differentiation. Furthermore, the histone modification signature of genes that remain bivalent in differentiated cells resolves into a cell cycle-independent pattern after lineage commitment. These results establish a new dimension of chromatin regulation important in the maintenance of pluripotencyhttp://mcb.asm.org/content/36/4/61

Radiofrequency ablation versus hepatic resection for hepatocellular carcinoma within the Milan criteria – A comparative study

AbstractBackgroundTo compare the results of radiofrequency ablation (RFA) with hepatic resection in the treatment of hepatocellular carcinoma (HCC) within the Milan criteria.MethodsA nonrandomized comparative study was performed with 111 consecutive patients who underwent laparoscopic RFA (n = 31) or curative hepatic resection (n = 80) for HCC within Milan criteria.ResultsProcedure related complications were less often and severe after RFA than resection (3.2% vs. 25%). There was no significant difference in hospital mortality (0% vs. 3.8%). Hospital stay was significantly shorter in the RFA group than in the resection group (mean, 3.8 vs. 6.8 days). The 1-, 3-, and 5-year disease-free survival rates for the RFA group and the resection group were 76%, 40%, 40% and 76%, 60%, 60%, respectively. Disease-free survival was significantly lower in the RFA group than in the resection group. The corresponding 1-, 3-, and 5-year overall survival rates for the RFA group and the resection group were 100%, 92%, 84%, and 92%, 75%, 71%, respectively. The overall survival for RFA and resection were not significantly different.ConclusionsOur result showed comparable overall survival between RFA and surgery, although RFA was associated with a significantly higher tumor recurrence rate. RFA had the advantages over surgical resection in being less invasive and having lower morbidity

D* Production in Deep Inelastic Scattering at HERA

This paper presents measurements of D^{*\pm} production in deep inelastic scattering from collisions between 27.5 GeV positrons and 820 GeV protons. The data have been taken with the ZEUS detector at HERA. The decay channel $D^{*+}\to (D^0 \to K^- \pi^+) \pi^+$ (+ c.c.) has been used in the study. The $e^+p$ cross section for inclusive D^{*\pm} production with $5<Q^2<100 GeV^2$ and $y<0.7$ is 5.3 \pms 1.0 \pms 0.8 nb in the kinematic region {$1.3<p_T(D^{*\pm})<9.0$ GeV and $| \eta(D^{*\pm}) |<1.5$}. Differential cross sections as functions of p_T(D^{*\pm}), $\eta(D^{*\pm}), W$ and $Q^2$ are compared with next-to-leading order QCD calculations based on the photon-gluon fusion production mechanism. After an extrapolation of the cross section to the full kinematic region in p_T(D^{*\pm}) and $\eta$(D^{*\pm}), the charm contribution $F_2^{c\bar{c}}(x,Q^2)$ to the proton structure function is determined for Bjorken $x$ between 2 $\cdot$ 10$^{-4}$ and 5 $\cdot$ 10$^{-3}$.Comment: 17 pages including 4 figure

Observation of hard scattering in photoproduction events with a large rapidity gap at HERA

Events with a large rapidity gap and total transverse energy greater than 5 GeV have been observed in quasi-real photoproduction at HERA with the ZEUS detector. The distribution of these events as a function of the $\gamma p$ centre of mass energy is consistent with diffractive scattering. For total transverse energies above 12 GeV, the hadronic final states show predominantly a two-jet structure with each jet having a transverse energy greater than 4 GeV. For the two-jet events, little energy flow is found outside the jets. This observation is consistent with the hard scattering of a quasi-real photon with a colourless object in the proton.Comment: 19 pages, latex, 4 figures appended as uuencoded fil

Observation of Events with an Energetic Forward Neutron in Deep Inelastic Scattering at HERA

In deep inelastic neutral current scattering of positrons and protons at the center of mass energy of 300 GeV, we observe, with the ZEUS detector, events with a high energy neutron produced at very small scattering angles with respect to the proton direction. The events constitute a fixed fraction of the deep inelastic, neutral current event sample independent of Bjorken x and Q2 in the range 3 · 10-4 \u3c xBJ \u3c 6 · 10-3 and 10 \u3c Q2 \u3c 100 GeV2

Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals

J. Kaprio, S. Ripatti ja M.-L. Lokki työryhmien jäseniä.Peer reviewe

The journal of Imperial and Commonwealth history

In creating a successful product it is important to understand consumers’ perceptions of a product early in the design process. Often, design students lack the necessary data collection and user testing skills to support effective design decision-making. Consequently, their products might not be acceptable to the intended consumers and are thus likely to fail in the marketplace. For design students to acquire those skills, design curricula should incorporate statistical courses teaching the concepts of data and user testing. We addressed this challenge by developing an automated tool named DACADE, assisting design students to systematically collect and analyze data. This paper reports the user acceptance study of DACADE designed to determine its level of user satisfaction and aesthetic appeal. The results confirmed a need for a formal introduction to systematic sampling, collection of performance data as well as of opinion data, data analysis, interpretation, and application of statistics to product design

A review on the existing visual tools for design students

This paper explores possible solutions to overcome the problem of design students lacking the skills and knowledge of user testing and data analysis to inform design decision-making that can help them to create successful products. A preliminary investigation and review is reported of existing visual interactive software tools intended to support design students and lecturers. Some of these tools might meet the requirements for teaching sampling methods (selecting suitable people and products) as well as testing techniques including data collection, analysis, and interpretation to design students. A discussion of existing visual software tools is presented first, followed by a dis

The design and evaluation of DACADE visual tool: Theoretical implications

A goal of every designer is to create successful products for consumers. In creating a successful product, it is crucial for a designer to understand consumers’ perceptions of a product early in the design process. Nevertheless, design students lack the necessary data collection and user testing skills to support effective design decision-making. Consequently, their products might not be acceptable to the intended consumers and are thus likely to fail in the marketplace. For design students to acquire those skills, design curricula should incorporate statistical courses teaching the concepts of data and user testing. We addressed this challenge by developing an automated visual tool named DACADE, assisting design students to systematically collect and analyze data. This paper reports the theoretical implications discovered during the process from designing through to implementing and evaluating DACADE concerning the transfer of learning, the appropriateness of graphics used in a software tool, and user motivation in a learning environment