Aims
We investigated the role of transient receptor potential vanilloid receptor type 1 (TRPV1) in simvastatin‐mediated activation of endothelial nitric oxide synthase (eNOS) and angiogenesis.
...Methods
Fluo‐8 NW assay was for Ca2+ detection; Griess's assay was for NO bioavailability; Western blotting and immunoprecipitation were for protein phosphorylation and interaction; tube formation and Matrigel plug assay were for angiogenesis.
Results
In endothelial cells (ECs), treatment with simvastatin time‐dependently increased intracellular level of Ca2+. Pharmacological inhibition or genetic disruption of TRPV1 abrogated simvastatin‐mediated elevation of intracellular Ca2+ in ECs or TRPV1‐transfected HEK293 cells. Loss of TRPV1 function abolished simvastatin‐induced NO production and phosphorylation of eNOS and calmodulin protein kinase II (CaMKII) in ECs and in aortas of mice. Inhibition of TRPV1 activation prevented the simvastatin‐elicited increase in the formation of TRPV1–Akt–CaMKII–AMPK–eNOS complex. In mice, Matrigel plug assay showed that simvastatin‐evoked angiogenesis was abolished by TRPV1 antagonist and genetic ablation of TRPV1. Additionally, our results demonstrated that TRP ankyrin 1 (TRPA1) is the downstream effector in the simvastatin‐activated TRPV1‐Ca2+ signalling and in the consequent NO production and angiogenesis as evidence by that re‐expression of TRPA1 further augmented simvastatin‐elicited Ca2+ influx in TRPV1‐expressed HEK293 cells and ablation of TRPA1 function profoundly inhibited the simvastatin‐induced increase in the phosphorylation of eNOS and CaMKII, formation of TRPV1–Akt–CaMKII–AMPK–eNOS complex, NO bioavailability, tube formation and angiogenesis in ECs or mice.
Conclusion
Simvastatin‐induced Ca2+ influx may through the activation of TRPV1–TRPA1 signalling, which leads to phosphorylation of CaMKII, increases in the formation of TRPV1–CaMKII–AMPK–eNOS complex, eNOS activation, NO production and, ultimately, angiogenesis in ECs.
The Korea Invisible Mass Search (KIMS) collaboration has developed low-background NaI(Tl) crystals that are suitable for the direct detection of WIMP dark matter. Building on experience accumulated ...during the KIMS-CsI programs, the KIMS-NaI experiment will consist of a 200 kg NaI(Tl) crystal array surrounded by layers of shielding structures and will be operated at the Yangyang underground laboratory. The goal is to provide an unambiguous test of the DAMA/LIBRA annual modulation signature. Measurements of six prototype crystals show progress in the reduction of internal contamination from radioisotopes. Based on our understanding of these measurements, we expect to achieve a background level in the final detector configuration that is less than 1 count/day/keV/kg for recoil energies around 2 keV. The annual modulation sensitivity for the KIMS-NaI experiment shows that an unambiguous 7
σ
test of the DAMA/LIBRA signature would be possible with a 600 kg year exposure with this system.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Introduction Preeclampsia (PE) is a leading cause of maternal and neonatal mortality and morbidity worldwide. However, the pathophysiology of this disease is not yet fully understood. MiRNA ...plays an important role in post-transcriptional gene regulation. Recent studies have suggested that dysregulation of miRNAs in placental tissue is involved in the pathogenesis of PE. Therefore, we investigated miRNA profiles in PE placenta to understand the miRNA function in PE pathogenesis. Methods MiRNA profiling was performed in 20 formalin-fixed and paraffin-embedded samples (10 placentas from severe PE and 10 from a control group). We used a hybridization-based microarray with a PNA-probe comprised of 158 miRNAs. Results Thirteen miRNAs (miR-92b, miR-197, miR-342-3p, miR-296-5p, miR-26b, miR-25, miR-296-3p, miR-26a, miR-198, miR-202, miR-191, miR-95, and miR-204) were significantly overexpressed and two miRNAs (miR-21 and miR-223) were underexpressed in PE compared with the control group. Among 15 differentially expressed miRNAs, miR-26b, miR-296-5p, and miR-223 were found to be consistent with results from previous studies. We identified 893 genes that were predicted by at least three of four computational algorithms. Target genes participated in several signaling pathways, adherens junction, focal adhesion, and regulation of the actin cytoskeleton. Conclusions Several miRNAs are found to be dysregulated in placentas of PE patients and they seem to be closely associated with the early pathogenesis of PE. Further study is necessary to develop tools for early detection and management.
Establishing the appropriate theoretical framework for unconventional superconductivity in the iron-based materials requires correct understanding of both the electron correlation strength and the ...role of Fermi surfaces. This fundamental issue becomes especially relevant with the discovery of the iron chalcogenide superconductors. Here, we use angle-resolved photoemission spectroscopy to measure three representative iron chalcogenides, FeTe0.56Se0.44, monolayer FeSe grown on SrTiO3 and K0.76Fe1.72Se2. We show that these superconductors are all strongly correlated, with an orbital-selective strong renormalization in the dxy bands despite having drastically different Fermi surface topologies. Furthermore, raising temperature brings all three compounds from a metallic state to a phase where the dxy orbital loses all spectral weight while other orbitals remain itinerant. These observations establish that iron chalcogenides display universal orbital-selective strong correlations that are insensitive to the Fermi surface topology, and are close to an orbital-selective Mott phase, hence placing strong constraints for theoretical understanding of iron-based superconductors.
The effect of anthropogenic aerosols on cloud droplet concentrations and radiative properties is the source of one of the largest uncertainties in the radiative forcing of climate over the industrial ...period. This uncertainty affects our ability to estimate how sensitive the climate is to greenhouse gas emissions. Here we perform a sensitivity analysis on a global model to quantify the uncertainty in cloud radiative forcing over the industrial period caused by uncertainties in aerosol emissions and processes. Our results show that 45 per cent of the variance of aerosol forcing since about 1750 arises from uncertainties in natural emissions of volcanic sulphur dioxide, marine dimethylsulphide, biogenic volatile organic carbon, biomass burning and sea spray. Only 34 per cent of the variance is associated with anthropogenic emissions. The results point to the importance of understanding pristine pre-industrial-like environments, with natural aerosols only, and suggest that improved measurements and evaluation of simulated aerosols in polluted present-day conditions will not necessarily result in commensurate reductions in the uncertainty of forcing estimates.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We present a background model for dark matter searches using an array of NaI(Tl) crystals in the COSINE-100 experiment that is located in the Yangyang underground laboratory. The model includes ...background contributions from both internal and external sources, including cosmogenic radionuclides and surface
210
Pb contamination. To build the model in the low energy region, with a threshold of 1 keV, we used a depth profile of
210
Pb contamination in the surface of the NaI(Tl) crystals determined in a comparison between measured and simulated spectra. We also considered the effect of the energy scale errors propagated from the statistical uncertainties and the nonlinear detector response at low energies. The 1.7 years COSINE-100 data taken between October 21, 2016 and July 18, 2018 were used for this analysis. Our Monte Carlo simulation provides a non-Gaussian peak around 50 keV originating from beta decays of bulk
210
Pb in a good agreement with the measured background. This model estimates that the activities of bulk
210
Pb and
3
H are dominating the background rate that amounts to an average level of
2.85
±
0.15
counts/day/keV/kg in the energy region of (1–6) keV, using COSINE-100 data with a total exposure of 97.7 kg
·
years.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A
bstract
Limits on the cross section for weakly interacting massive particles (WIMPs) elastic scattering on nuclei in NaI(Tl) detectors at the Yangyang Underground Laboratory are obtained from a ...2967.4 kg·day data exposure. The nuclei recoiling from the scattering process are identified by the pulse shape of the scintillation light signals that they produce. The data are consistent with a no nuclear-recoil hypothesis, and WIMP-mass-dependent 90% confidence-level upper-limits are set on WIMP-nuclei elastic scattering cross sections. These limits partially exclude the DAMA/LIBRA allowed region for WIMP-sodium interactions with the same NaI(Tl) target material. The 90% confidence level upper limit on the WIMP-nucleon spin-independent cross section is 3.26×10
−4
pb for a WIMP mass of 10 GeV/c
2
.
The annual modulation signal observed by the DAMA experiment is a long-standing question in the community of dark matter direct detection. This necessitates an independent verification of its ...existence using the same detection technique. The COSINE-100 experiment has been operating with 106 kg of low-background NaI(Tl) detectors providing interesting checks on the DAMA signal. However, due to higher backgrounds in the NaI(Tl) crystals used in COSINE-100 relative to those used for DAMA, it was difficult to reach final conclusions. Since the start of COSINE-100 data taking in 2016, we also have initiated a program to develop ultra-pure NaI(Tl) crystals for COSINE-200, the next phase of the experiment. The program includes efforts of raw powder purification, ultra-pure NaI(Tl) crystal growth, and detector assembly techniques. After extensive research and development of NaI(Tl) crystal growth, we have successfully grown a few small-size (0.61–0.78 kg) thallium-doped crystals with high radio-purity. A high light yield has been achieved by improvements of our detector assembly technique. Here we report the ultra-pure NaI(Tl) detector developments at the Institute for Basic Science, Korea. The technique developed here will be applied to the production of NaI(Tl) detectors for the COSINE-200 experiment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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