BackgroundWe previously identified TrkB as an oncogene involved in promoting metastasis in endometrial carcinoma (EC). Here, we sought to delineate the effect of changes in TrkB expression on the global profile of microRNAs (miRNAs) in EC cells and further investigated the correlation between the expression of certain miRNA and TrkB in the clinicopathologic characteristics of EC patients.Methods and resultsUsing quantitative reverse transcription-PCR (qRT-PCR), we found that expression of TrkB mRNA has no significant difference in transcript levels between normal endometrium and EC cells captured by laser capture microdissection, while immunohistochemistry results demonstrated a markedly higher expression of TrkB protein in EC tissues. The microRNA array showed that ectopic overexpression and knockdown of TrkB expression caused global changes in miRNA expression in EC cells. qRT-PCR results showed that elevated TrkB repressed miR-204-5p expression in EC cells. Furthermore, immunoblotting assays revealed that TrkB overexpression in IshikawaTrkB cells noticeably increased JAK2 and STAT3 phosphorylation, which, however, was aborted by TrkB knockdown in HEC-1BshTrkB cells. Moreover, ChIP assays showed that phospho-STAT3 could directly bind to STAT3-binding sites near the TRPM3 promoter region upstream of miR-204-5p. Interestingly, using bioinformatics analysis and luciferase assays, we identified TrkB was a novel target of miR-204-5p. Functionally, the MTT assays, clonogenic and Transwell assays showed that miR-204-5p significantly suppressed the clonogenic growth, migration and invasion of EC cells. Furthermore, miR-204-5p also inhibited the growth of tumor xenografts bearing human EC cells. Importantly, we found lower miR-204-5p expression was associated with advanced FIGO stages, lymph node metastasis and probably a lower chance for survival in EC patients.ConclusionsThis study uncovers a new regulatory loop involving TrkB/miR-204-5p that is critical to the tumorigenesis of EC and proposes that reestablishment of miR-204-5p expression could be explored as a potential new therapeutic target for this disease.
PSRJ2021+4026 showed a sudden decrease in the gamma-ray emission at the glitch that occurred around 2011 October 16, and a relaxation of the flux to the pre-glitch state at around 2014 December. We report X-ray analysis results of the data observed by XMM-Newton on 2015 December 20 in the post-relaxation state. To examine any change in the X-ray emission, we compare the properties of the pulse profiles and spectra at the low gamma-ray flux state and at the post-relaxation state. The phase-averaged spectra for both states can be well described by a power-law component plus a blackbody component. The former is dominated by unpulsed emission and probably originated from the pulsar wind nebula as reported by Hui et al. The emission property of the blackbody component is consistent with the emission from the polar cap heated by the back-flow bombardment of the highenergy electrons or positrons that were accelerated in the magnetosphere. We found no significant change in the X-ray emission properties between two states. We suggest that the change of the X-ray luminosity is at an order of ∼4%, which is difficult to measure with the current observations. We model the observed X-ray light curve with the heated polar cap emission, and we speculate that the observed large pulsed fraction is owing to asymmetric magnetospheric structure.
PSR J2021+4026 is a radio-quiet gamma-ray pulsar and the first pulsar that shows state change of the gamma-ray emission and spindown rate. The state change of PSR J2021+4026 was first observed at 2011 October, at which the pulsar changes the state from high gamma-ray flux/low spindown rate state to low gamma-ray flux/high spindown rate state. In 2014 December, PSR J2021+4026 recovered the state before the 2011 state change over a timescale of a few months. We report that the long-term evolution of the gamma-ray flux and timing behavior suggests that PSR J2021+4026 changed the state near 2018 February 1 and entered a new low gamma-ray flux/high spindown rate state. At the 2018 state change, the averaged flux dropped from (1.29 ± 0.01) × 10−6 cts cm−2 s−1 to (1.12 ± 0.01) × 10−6 cts cm−2 s−1, which is behavior similar to that of the 2011 event. The spindown rate has increased by ∼3% in the new state since the 2018 state change. The shapes of pulse profile and spectrum in GeV bands also changed at the 2018 event, and they are consistent with behavior at the 2011 state change. Our results probably suggest that PSR J2021+4026 is switching between different states with a timescale of several years, like some radio pulsars (e.g., PSR B1828-11). PSR J2021+4026 will provide a unique opportunity to study the mechanism of the state switching.
This study explores the impact of a STEM integration teacher professional development program focusing on teachers' perception of engineering and their attitudes toward integrating engineering into teaching. A total of sixty-eight teachers from ten schools participated in the program for five days. Data are collected from three main sources including (1) pre and post concept maps probing teachers' perceptions about the engineering discipline, (2) a pre and post survey measuring teachers' self-efficacy of teaching science/mathematics within the engineering context, and (3) engineering integrated science and (or) mathematics lesson plans and teaching reflections. This study utilizes both qualitative and quantitative research methods depending on the data we have collected. The results show that both science and math teachers thought that integrating engineering into teaching provided valuable outcomes, i.e., promoting students' learning about engineering and improving their interest in science or math through real-world problem solving exercises. Participants also felt more comfortable about integrating engineering in their teaching after the program. The results also imply that the teachers' understandings of engineering become more concrete after the program. This study also provides an overview of the challenges and advantages of teaching engineering in K-12 science and mathematics classrooms.
The high magnetic field pulsar PSR J1119−6127, detected from radio to high-energy wavelengths, underwent a magnetar-like outburst beginning on 2016 July 27. In this paper, we study the postoutburst multiwavelength properties of this pulsar from the radio to GeV bands and discuss its similarity with the outburst of the magnetar XTE J1810−197. In phase-resolved spectral analysis of 0.5–10 keV X-ray data collected in 2016 August, the on- and off-pulse spectra are both characterized by two blackbody components and also require a power-law component similar to the hard X-ray spectra of magnetars. This power-law component is no longer distinguishable in data from 2016 December. We likewise find that there was no substantial shift between the radio and X-ray pulse peaks after the 2016 X-ray outburst. The gamma-ray pulsation after the X-ray outburst is confirmed with data taken after 2016 December, and the pulse structure and phase difference between the gamma-ray and radio peaks (∼0.4 cycle) are also consistent with those before the X-ray outburst. These multiwavelength observations suggest that the reconfiguration of the global magnetosphere after the 2016 magnetar-like outburst continued for at most about 6 months. We discuss the evolution of the X-ray emission after the 2016 outburst with the untwisting magnetosphere model.
Practitioners and researchers in geoscience education embrace collaboration applying ICON (Integrated, Coordinated, Open science, and Networked) principles and approaches which have been used to create and share large collections of educational resources, to move forward collective priorities, and to foster peer-learning among educators. These strategies can also support the advancement of coproduction between geoscientists and diverse communities. For this reason, many authors from the geoscience education community have co-created three commentaries on the use and future of ICON in geoscience education. We envision that sharing our expertise with ICON practice will be useful to other geoscience communities seeking to strengthen collaboration. Geoscience education brings substantial expertise in social science research and its application to building individual and collective capacity to address earth sustainability and equity issues at local to global scales The geoscience education community has expanded its own ICON capacity through access to and use of shared resources and research findings, enhancing data sharing and publication, and leadership development. We prioritize continued use of ICON principles to develop effective and inclusive communities that increase equity in geoscience education and beyond, support leadership and full participation of systemically non-dominant groups and enable global discussions and collaborations. Plain Language SummaryThe Geoscience Education community describes the value, use, and future of ICON collaboration through three independent, community-produced commentaries focused on the practice of geoscience education; geoscience education research; and diversity, equity, inclusion, and justice.
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