63 research outputs found

    Of mice and men: molecular genetics of congenital heart disease

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    Identification of a novel non-sense mutation in TBX5 gene in pediatric patients with congenital heart defects

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    A CASE OF TRUNCUS ARTERIOSUS

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    Seismicity associated with the 1991-1995 dome growth at Unzen Volcano

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    From May 1991 until February 1995, seismicity in the crater area of Unzen Volcano, southwest Japan, intensified in conjunction with the growth of a dacite lava dome. We used data from seismic stations located near the crater to identify approximately 580,000 summit earthquakes with maximum amplitudes equal to or greater than 1 × 10- 3 cm/s. The temporal characteristics of the seismicity level were different for exogenous and endogenous periods of dome growth. Periods of solely exogenous growth were accompanied by several days or weeks of increased seismicity, and levels of seismicity were notably reduced between successive seismically active periods. In contrast, levels of seismicity were generally high during periods when the dome grew endogenously, with repeated cycles of increasing and decreasing seismicity of one to two months duration. We classified the waveforms of summit earthquakes into high-frequency (HF), medium-frequency (MF), and low-frequency (LF) types on the basis of spectral analysis. Dominant waveform types varied significantly over time: HF was dominant in May 1991, LF from June 1991 until August 1993, MF during September and October 1993, and HF and MF from November 1993. HF and MF events are mainly distributed at depths of 500-1100 m above sea level (ASL), just below the lava dome, while LF events are widely distributed at depths from 500 m ASL to the interior of the dome itself. To efficiently detect earthquake families, we conducted a cross-correlation analysis of waveforms. Using the events one-by-one as reference events, we calculated peak correlation coefficients between each reference event and events that occurred within 24 h either side of the reference event. The results show that many earthquake families of all waveform types occurred throughout the growth period of the dome. The durations of most families were less than two weeks and were not related to the intensity of seismic activity. The incidence rate of events within each family reached a peak in the middle of the respective activity period. The results also suggest that the waveforms in several analyzed families gradually evolved over time. During periods when HF events intensified, several families appeared contemporaneously. In contrast, during periods when LF events intensified, the occurrence pattern of earthquake families was relatively simple: a new family became active only once the activity of the previous family had declined or ceased completely. A possible source mechanism for families of HF events is stick-slip within the stiff rocks surrounding the conduit; however, several different types of source mechanisms should be considered for families of LF events

    Microfluidic single-cell analysis of transplanted human induced pluripotent stem cell-derived cardiomyocytes after acute myocardial infarction

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    BACKGROUND: Human induced pluripotent stem cells (iPSCs) are attractive candidates for therapeutic use, with the potential to replace deficient cells and to improve functional recovery in injury or disease settings. Here, we test the hypothesis that human iPSC-derived cardiomyocytes (iPSC-CMs) can secrete cytokines as a molecular basis to attenuate adverse cardiac remodeling after myocardial infarction. METHODS AND RESULTS: Human iPSCs were generated from skin fibroblasts and differentiated in vitro with a small molecule-based protocol. Troponin(+) iPSC-CMs were confirmed by immunohistochemistry, quantitative polymerase chain reaction, fluorescence-activated cell sorting, and electrophysiological measurements. Afterward, 2×10(6) iPSC-CMs derived from a cell line transduced with a vector expressing firefly luciferase and green fluorescent protein were transplanted into adult NOD/SCID mice with acute left anterior descending artery ligation. Control animals received PBS injection. Bioluminescence imaging showed limited engraftment on transplantation into ischemic myocardium. However, magnetic resonance imaging of animals transplanted with iPSC-CMs showed significant functional improvement and attenuated cardiac remodeling compared with PBS-treated control animals. To understand the underlying molecular mechanism, microfluidic single-cell profiling of harvested iPSC-CMs, laser capture microdissection of host myocardium, and in vitro ischemia stimulation were used to demonstrate that the iPSC-CMs could release significant levels of proangiogenic and antiapoptotic factors in the ischemic microenvironment. CONCLUSIONS: Transplantation of human iPSC-CMs into an acute mouse myocardial infarction model can improve left ventricular function and attenuate cardiac remodeling. Because of limited engraftment, most of the effects are possibly explained by paracrine activity of these cells
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