lncRNAs play important roles in the epigenetic regulation of carcinogenesis and progression. Previous studies suggest that HOTAIR contributes to gastric cancer (GC) development, and the ...overexpression of HOTAIR predicts a poor prognosis. In this study, we found that HOTAIR was more highly expressed in diffuse-type GC than in intestinal type (P=0.048). In the diffuse type, there is significant relationship between HOTAIR expression and DFS (P<0.001). CDH1 was downregulated in diffuse-type GC tissues (P=0.0007) and showed a negative relationship with HOTAIR (r(2)=0.154, P=0.0354). In addition, HOTAIR knockdown significantly repressed migration, invasion and metastasis both in vitro and vivo and reversed the epithelial-to-mesenchymal transition in GC cells. We also showed that HOTAIR recruiting and binding to PRC2 epigenetically represses miR34a, which controls the targets C-Met (HGF/C-Met/Snail pathway) and Snail, thus contributing to GC cell-EMT process and accelerating tumor metastasis. Moreover, it is demonstrated that HOTAIR crosstalk with microRNAs during epigenetic regulation. Our results suggest that HOTAIR acts as an EMT regulator and may be a candidate prognostic biomarker and a target for new therapies in GC patients.
An intense laser field can remove an electron from an atom or molecule and pull the electron into a large-amplitude oscillation in which it repeatedly collides with the charged core it left behind. ...Such recollisions result in the emission of very energetic photons by means of high-order-harmonic generation, which has been observed in atomic and molecular gases as well as in a bulk crystal. An exciton is an atom-like excitation of a solid in which an electron that is excited from the valence band is bound by the Coulomb interaction to the hole it left behind. It has been predicted that recollisions between electrons and holes in excitons will result in a new phenomenon: high-order-sideband generation. In this process, excitons are created by a weak near-infrared laser of frequency f(NIR). An intense laser field at a much lower frequency, f(THz), then removes the electron from the exciton and causes it to recollide with the resulting hole. New emission is predicted to occur as sidebands of frequency f(NIR) + 2nf(THz), where n is an integer that can be much greater than one. Here we report the observation of high-order-sideband generation in semiconductor quantum wells. Sidebands are observed up to eighteenth order (+18f(THz), or n = 9). The intensity of the high-order sidebands decays only weakly with increasing sideband order, confirming the non-perturbative nature of the effect. Sidebands are strongest for linearly polarized terahertz radiation and vanish when the terahertz radiation is circularly polarized. Beyond their fundamental scientific significance, our results suggest a new mechanism for the ultrafast modulation of light, which has potential applications in terabit-rate optical communications.
A search for millicharged particles, a simple extension of the standard model, has been performed with the ArgoNeuT detector exposed to the Neutrinos at the Main Injector beam at Fermilab. The ...ArgoNeuT liquid argon time projection chamber detector enables a search for millicharged particles through the detection of visible electron recoils. We search for an event signature with two soft hits (MeV-scale energy depositions) aligned with the upstream target. For an exposure of the detector of 1.0×10^{20} protons on target, one candidate event has been observed, compatible with the expected background. This search is sensitive to millicharged particles with charges between 10^{-3}e and 10^{-1}e and with masses in the range from 0.1 to 3 GeV. This measurement provides leading constraints on millicharged particles in this large unexplored parameter space region.
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Melatonin and its receptors have been detected in the ovary of many species, and mediate ovarian functions. The present study was designed to investigate the expression and subcellar location of ...melatonin receptors in bovine granulosa cells (GCs), using reverse transcription (RT) polymerase chain reaction, Western blot, and immunofluorescence analyses. Furthermore, expression level of melatonin receptors mRNA (real-time polymerase chain reaction) after treatment with various concentrations of melatonin, as well as its effects on cell apoptosis, proliferation, and steroidogenesis (by flow cytometry and RIA), were determined. In bovine GCs, melatonin receptors MT1 and MT2 were differentially located at the cell membrane, the cytoplasm, and nuclear membranes. The expression of MT1 and MT2 mRNA was regulated differently by melatonin in time- and dose-dependent manners. Exogenous melatonin suppressed cell apoptosis (P < 0.05) but not proliferation (P > 0.05). After 72 h, the apoptotic rate was significantly inhibited in all treatment groups. Meanwhile, melatonin supplementation stimulated progesterone production, but inhibited estradiol biosynthesis, in a time-dependent manner. Progesterone production was highest (P < 0.05) at 72 h. Estradiol concentrations were almost unaffected (P > 0.05) at 24 h, but were decreased (P < 0.05) at 48 h. In conclusion, exogenous melatonin acts via receptors and has important roles in regulation of development and function of bovine GCs.
The Whole Atmosphere Community Climate Model version 6 (WACCM6) is a major update of the whole atmosphere modeling capability in the Community Earth System Model (CESM), featuring enhanced physical, ...chemical and aerosol parameterizations. This work describes WACCM6 and some of the important features of the model. WACCM6 can reproduce many modes of variability and trends in the middle atmosphere, including the quasi‐biennial oscillation, stratospheric sudden warmings, and the evolution of Southern Hemisphere springtime ozone depletion over the twentieth century. WACCM6 can also reproduce the climate and temperature trends of the 20th century throughout the atmospheric column. The representation of the climate has improved in WACCM6, relative to WACCM4. In addition, there are improvements in high‐latitude climate variability at the surface and sea ice extent in WACCM6 over the lower top version of the model (CAM6) that comes from the extended vertical domain and expanded aerosol chemistry in WACCM6, highlighting the importance of the stratosphere and tropospheric chemistry for high‐latitude climate variability.
Plain Language Summary
This manuscript describes the Whole Atmosphere Community Climate Model Version 6 (WACCM6), a chemistry and climate model which extends up to 140 km in the upper atmosphere. WACCM6 reproduces many important features of the climate system, and the addition of detailed chemistry and the higher than normal model top produces slightly improved simulations of the Arctic region.
Key Points
WACCM6 is a major upgrade to previous versions
WACCM6 can reproduce many modes of variability and trends in the middle atmosphere
WACCM6 provides improvements in high‐latitude climate variability at the surface and sea ice extent over a low top model
Recent reports have highlighted the challenge of keeping global average temperatures below 2 °C and-even more so-1.5 °C (IPCC 2018). Fossil-fuel burning and cement production release ∼90% of all CO2 ...emissions from human activities. After a three-year hiatus with stable global emissions (Jackson et al 2016; Le Quéré C et al 2018a ; IEA 2018), CO2 emissions grew by 1.6% in 2017 to 36.2 Gt (billion tonnes), and are expected to grow a further 2.7% in 2018 (range: 1.8%-3.7%) to a record 37.1 2 Gt CO2 (Le Quéré et al 2018b). Additional increases in 2019 remain uncertain but appear likely because of persistent growth in oil and natural gas use and strong growth projected for the global economy. Coal use has slowed markedly in the last few years, potentially peaking, but its future trajectory remains uncertain. Despite positive progress in ∼19 countries whose economies have grown over the last decade and their emissions have declined, growth in energy use from fossil-fuel sources is still outpacing the rise of low-carbon sources and activities. A robust global economy, insufficient emission reductions in developed countries, and a need for increased energy use in developing countries where per capita emissions remain far below those of wealthier nations will continue to put upward pressure on CO2 emissions. Peak emissions will occur only when total fossil CO2 emissions finally start to decline despite growth in global energy consumption, with fossil energy production replaced by rapidly growing low- or no-carbon technologies.
β‐hydroxybutyric acid (BHBA) has recently been shown to regulate hormone synthesis and secretion in the hypothalamus. However, little is known about the effects of BHBA‐mediated hormone regulation or ...the detailed mechanisms by which BHBA regulates growth hormone‐releasing hormone (GHRH) synthesis and secretion. In the present study, we examined the expression of the BHBA receptor GPR109A in primary hypothalamic cell cultures. We hypothesised that BHBA regulates GHRH via GPR109A and its downstream signals. Initial in vivo studies conducted in rats demonstrated that GHRH mRNA expression in the hypothalamus was strongly inversely correlated with BHBA levels in the cerebrospinal fluid during postnatal development (r = −0.89, P < 0.01). Furthermore, i.c.v. administration of BHBA acutely decreased GHRH mRNA expression in rats. Further in vitro studies revealed a decrease in GHRH synthesis and secretion in primary hypothalamic cells after treatment with BHBA; this effect was inhibited when hypothalamic cells were pretreated with pertussis toxin (PTX). BHBA had no effect on GHRH synthesis and secretion in GT1‐7 cells, which do not exhibit cell surface expression of GPR109A. Furthermore, BHBA acutely decreased the transcription of the homeobox gene for Gsh‐1 in the hypothalamus in both in vivo and in vitro, and this effect was also inhibited by PTX in vitro. In primary hypothalamic cells, BHBA activated the extracellular signal‐regulated kinase (ERK)1/2, p38 and c‐Jun N‐terminal kinase mitogen‐activated protein kinase (MAPK) kinases, as shown by western blot analysis. Moreover, inhibition of ERK1/2 with U0126 attenuated the BHBA‐mediated reduction in Gsh‐1 expression and GHRH synthesis and secretion. These results strongly suggest that BHBA directly regulates GHRH synthesis and secretion via the GPR109A/ERK1/2 MAPK pathway, and also that Gsh‐1 is essential for this function.
Highlights • Regional and network functional changes could be seen in the early stage of SCI. • Functional changes were associated with clinical symptom severity in SCI patients. • Functional ...reorganization may reflect a compensatory role in the recovery of SCI.
Abstract
The recently discovered kagome superconductors
A
V
3
Sb
5
(
A
= K, Rb, Cs) exhibit unusual charge-density-wave (CDW) orders with time-reversal and rotational symmetry breaking. One of the ...most crucial unresolved issues is identifying the symmetry of the superconductivity that develops inside the CDW phase. Theory predicts a variety of unconventional superconducting symmetries with sign-changing and chiral order parameters. Experimentally, however, superconducting phase information in
A
V
3
Sb
5
is still lacking. Here we report the impurity effects in CsV
3
Sb
5
using electron irradiation as a phase-sensitive probe of superconductivity. Our magnetic penetration depth measurements reveal that with increasing impurities, an anisotropic fully-gapped state changes to an isotropic full-gap state without passing through a nodal state. Furthermore, transport measurements under pressure show that the double superconducting dome in the pressure-temperature phase diagram survives against sufficient impurities. These results support that CsV
3
Sb
5
is a non-chiral, anisotropic
s
-wave superconductor with no sign change both at ambient and under pressure.
To bridge the gap between two-dimensional cell culture and tissue, various three-dimensional (3-D) cell culture approaches have been developed for the investigation of cardiac myocytes (CMs) and ...cardiac fibroblasts (CFs). However, several limitations still exist. This study was designed to develop a cardiac 3-D culture model with a scaffold-free technology that can easily and inexpensively generate large numbers of microtissues with cellular distribution and functional behavior similar to cardiac tissue. Using micromolded nonadhesive agarose hydrogels containing 822 concave recesses (800 μm deep × 400 μm wide), we demonstrated that neonatal rat ventricular CMs and CFs alone or in combination self-assembled into viable (Live/Dead stain) spherical-shaped microtissues. Importantly, when seeded simultaneously or sequentially, CMs and CFs self-sorted to be interspersed, reminiscent of their myocardial distribution, as shown by cell type-specific CellTracker or antibody labeling. Microelectrode recordings and optical mapping revealed characteristic triangular action potentials (APs) with a resting membrane potential of -66 ± 7 mV (n = 4) in spontaneously contracting CM microtissues. Under pacing, optically mapped AP duration at 90% repolarization and conduction velocity were 100 ± 30 ms and 18.0 ± 1.9 cm/s, respectively (n = 5 each). The presence of CFs led to a twofold AP prolongation in heterogenous microtissues (CM-to-CF ratio of 1:1). Importantly, Ba(2+)-sensitive inward rectifier K(+) currents and Ca(2+)-handling proteins, including sarco(endo)plasmic reticulum Ca(2+)-ATPase 2a, were detected in CM-containing microtissues. Furthermore, cell type-specific adenoviral gene transfer was achieved, with no impact on microtissue formation or cell viability. In conclusion, we developed a novel scaffold-free cardiac 3-D culture model with several advancements for the investigation of CM and CF function and cross-regulation.
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