Strict De Novo Methylation of the 35S Enhancer Sequence in Gentian

A novel transgene silencing phenomenon was found in the ornamental plant, gentian (Gentiana triflora × G. scabra), in which the introduced Cauliflower mosaic virus (CaMV) 35S promoter region was strictly methylated, irrespective of the transgene copy number and integrated loci. Transgenic tobacco having the same vector did not show the silencing behavior. Not only unmodified, but also modified 35S promoters containing a 35S enhancer sequence were found to be highly methylated in the single copy transgenic gentian lines. The 35S core promoter (−90)-introduced transgenic lines showed a small degree of methylation, implying that the 35S enhancer sequence was involved in the methylation machinery. The rigorous silencing phenomenon enabled us to analyze methylation in a number of the transgenic lines in parallel, which led to the discovery of a consensus target region for de novo methylation, which comprised an asymmetric cytosine (CpHpH; H is A, C or T) sequence. Consequently, distinct footprints of de novo methylation were detected in each (modified) 35S promoter sequence, and the enhancer region (−148 to −85) was identified as a crucial target for de novo methylation. Electrophoretic mobility shift assay (EMSA) showed that complexes formed in gentian nuclear extract with the −149 to −124 and −107 to −83 region probes were distinct from those of tobacco nuclear extracts, suggesting that the complexes might contribute to de novo methylation. Our results provide insights into the phenomenon of sequence- and species- specific gene silencing in higher plants

Possibility of multivariate function composed of plasma amino acid profiles as a novel screening index for non-small cell lung cancer: a case control study

<p>Abstract</p> <p>Background</p> <p>The amino-acid balance in cancer patients often differs from that in healthy individuals, because of metabolic changes. This study investigated the use of plasma amino-acid profiles as a novel marker for screening non-small-cell lung cancer (NSCLC) patients.</p> <p>Methods</p> <p>The amino-acid concentrations in venous blood samples from pre-treatment NSCLC patients (<it>n </it>= 141), and age-matched, gender-matched, and smoking status-matched controls (<it>n </it>= 423), were measured using liquid chromatography and mass spectrometry. The resultant study data set was subjected to multiple logistic regression analysis to identify amino acids related with NSCLC and construct the criteria for discriminating NSCLC patients from controls. A test data set derived from 162 patients and 3,917 controls was used to validate the stability of the constructed criteria.</p> <p>Results</p> <p>The plasma amino-acid profiles significantly differed between the NSCLC patients and the controls. The obtained model (including alanine, valine, isoleucine, histidine, tryptophan and ornithine concentrations) performed well, with an area under the curve of the receiver-operator characteristic curve (ROC_AUC) of >0.8, and allowed NSCLC patients and controls to be discriminated regardless of disease stage or histological type.</p> <p>Conclusions</p> <p>This study shows that plasma amino acid profiling will be a potential screening tool for NSCLC.</p

Impact of cardiac support device combined with slow-release prostacyclin agonist in a canine ischemic cardiomyopathy model

BackgroundThe cardiac support device supports the heart and mechanically reduces left ventricular (LV) diastolic wall stress. Although it has been shown to halt LV remodeling in dilated cardiomyopathy, its therapeutic efficacy is limited by its lack of biological effects. In contrast, the slow-release synthetic prostacyclin agonist ONO-1301 enhances reversal of LV remodeling through biological mechanisms such as angiogenesis and attenuation of fibrosis. We therefore hypothesized that ONO-1301 plus a cardiac support device might be beneficial for the treatment of ischemic cardiomyopathy.MethodsTwenty-four dogs with induced anterior wall infarction were assigned randomly to 1 of 4 groups at 1 week postinfarction as follows: cardiac support device alone, cardiac support device plus ONO-1301 (hybrid therapy), ONO-1301 alone, or sham control.ResultsAt 8 weeks post-infarction, LV wall stress was reduced significantly in the hybrid therapy group compared with the other groups. Myocardial blood flow, measured by positron emission tomography, and vascular density were significantly higher in the hybrid therapy group compared with the cardiac support device alone and sham groups. The hybrid therapy group also showed the least interstitial fibrosis, the greatest recovery of LV systolic and diastolic functions, assessed by multidetector computed tomography and cardiac catheterization, and the lowest plasma N-terminal pro-B-type natriuretic peptide levels (P < .05).ConclusionsThe combination of a cardiac support device and the prostacyclin agonist ONO-1301 elicited a greater reversal of LV remodeling than either treatment alone, suggesting the potential of this hybrid therapy for the clinical treatment of ischemia-induced heart failure

Sign of inverse spin Hall voltages generated by ferromagnetic resonance and temperature gradients in yttrium iron garnet|platinum bilayers

We carried out a concerted effort to determine the absolute sign of the inverse spin Hall effect voltage generated by spin currents injected into a normal metal. We focus on yttrium iron garnet (YIG)|platinum bilayers at room temperature, generating spin currents by microwaves and temperature gradients. We find consistent results for different samples and measurement setups that agree with theory. We suggest a right-hand-rule to define a positive spin Hall angle corresponding to with the voltage expected for the simple case of scattering of free electrons from repulsive Coulomb charges.Comment: incorporated additions from the published versio

Efficient spin transport in a paramagnetic insulator

The discovery of new materials that efficiently transmit spin currents has been important for spintronics and material science. The electric insulator $\mathrm{Gd}_3\mathrm{Ga}_5\mathrm{O}_{12}$ (GGG) is a superior substrate for growing magnetic films, but has never been considered as a conduit for spin currents. Here we report spin current propagation in paramagnetic GGG over several microns. Surprisingly, the spin transport persists up to temperatures of 100 K $\gg$ $T_{\mathrm{g}} = 180$ mK, GGG's magnetic glass-like transition temperature. At 5 K we find a spin diffusion length ${\lambda_{\mathrm{GGG}}} = 1.8 \pm 0.2 {\mu}$m and a spin conductivity ${\sigma}_{\mathrm{GGG}} = (7.3 \pm 0.3) \times10^4$ $\mathrm{Sm}^{-1}$ that is larger than that of the record quality magnet $\mathrm{Y}_3\mathrm{Fe}_5\mathrm{O}_{12}$ (YIG). We conclude that exchange coupling is not required for efficient spin transport, which challenges conventional models and provides new material-design strategies for spintronic devices.Comment: 21 pages, 4 figure

Dynamic Trend of Myocardial Edema in Takotsubo Syndrome: A Serial Cardiac Magnetic Resonance Study

BACKGROUND The wall motion abnormalities of the left ventricle (LV) in takotsubo syndrome (TTS) are known to be transient and completely recover within a few weeks. However, there is little information about the relationship between functional recovery and tissue characteristics. The aim of this study was to investigate the recovery process of TTS using cardiovascular magnetic resonance (CMR). METHODS Consecutive patients with TTS were prospectively enrolled. We performed serial CMR in the acute phase (<72 h after admission), the subacute phase (7-10 days after admission) and the chronic phase (3 months later). To assess the degree of myocardial edema quantitatively, we evaluated the signal intensity of myocardium on T2-weighted images and calculated the signal intensity ratio compared with the skeletal muscle. RESULTS Fifteen patients with TTS were enrolled. CMR demonstrated reduced LV ejection fraction in the acute phase, and it recovered almost completely by the subacute phase. On the other hand, severe myocardial edema was still observed in the subacute phase, associated with increased LV mass. The highest signal intensity ratio in the subacute phase was correlated with the maximum voltage of negative T wave on electrocardiogram (r = 0.57, p = 0.03). CONCLUSIONS In patients with TTS, myocardial edema associated with increased LV mass still remained in the subacute phase despite functional recovery of the LV. Electrocardiogram may be useful to assess the degree of myocardial edema in the subacute phase. Our study suggests that myocardial ischemia might have a central role in developing TTS

Observation of nuclear-spin Seebeck effect

Thermoelectric effects have been applied to power generators and temperature sensors that convert waste heat into electricity. The effects, however, have been limited to electrons to occur, and inevitably disappear at low temperatures due to electronic entropy quenching. Here, we report thermoelectric generation caused by nuclear spins in a solid: nuclear-spin Seebeck effect. The sample is a magnetically ordered material MnCO3 having a large nuclear spin (I = 5/2) of 55Mn nuclei and strong hyperfine coupling, with a Pt contact. In the system, we observe low-temperature thermoelectric signals down to 100 mK due to nuclear-spin excitation. Our theoretical calculation in which interfacial Korringa process is taken into consideration quantitatively reproduces the results. The nuclear thermoelectric effect demonstrated here offers a way for exploring thermoelectric science and technologies at ultralow temperaturesThis work was supported by JST ERATO “Spin Quantum Rectification Project” (JPMJER1402), JST CREST (JPMJCR20C1 and JPMJCR20T2), JSPS KAKENHI (JP19H05600, JP19K21031, JP20H02599, JP20K22476, and JP20K15160), MEXT [Innovative Area “Nano Spin Conversion Science” (JP26103005)], and Daikin Industries, Ltd. The work at UCLA was supported by the US Department of Energy, Office of Basic Energy Sciences under Award number DE-SC0012190. K.O. acknowledges support from GP-Spin at Tohoku University. R.R. acknowledges support from the European Commission through the project 734187-SPICOLOST (H2020-MSCA-RISE-2016), the European Union’s Horizon 2020 research and innovation program through the Marie Sklodowska-Curie Actions grant agreement SPEC number 894006 and the Spanish Ministry of Science (RYC 2019-026915-I)S