The deubiquitinating enzyme MINDY2 promotes pancreatic cancer proliferation and metastasis by stabilizing ACTN4 expression and activating the PI3K/AKT/mTOR signaling pathway

The pathogenic mechanisms of pancreatic cancer (PC) are still not fully understood. Ubiquitination modifications have a crucial role in tumorigenesis and progression. Yet, the role of MINDY2, a member of the motif interacting with Ub-containing novel DUB family (MINDY), as a newly identified deubiquitinating enzyme, in PC is still unclear. In this study, we found that MINDY2 expression is elevated in PC tissue (clinical samples) and was associated with poor prognosis. We also found that MINDY2 is associated with pro-carcinogenic factors such as epithelial-mesenchymal transition (EMT), inflammatory response, and angiogenesis; the ROC curve suggested that MINDY2 has a high diagnostic value in PC. Immunological correlation analysis suggested that MINDY2 is deeply involved in immune cell infiltration in PC and is associated with immune checkpoint-related genes. In vivo and in vitro experiments further suggested that elevated MINDY2 promotes PC proliferation, invasive metastasis, and EMT. Meanwhile, actinin alpha 4 (ACTN4) was identified as a MINDY2-interacting protein by mass spectrometry and other experiments, and ACTN4 protein levels were significantly correlated with MINDY2 expression. The ubiquitination assay confirmed that MINDY2 stabilizes the ACTN4 protein level by deubiquitination. The pro-oncogenic effect of MINDY2 was significantly inhibited by silencing ACTN4. Bioinformatics Analysis and Western blot experiments further confirmed that MINDY2 stabilizes ACTN4 through deubiquitination and thus activates the PI3K/AKT/mTOR signaling pathway. In conclusion, we identified the oncogenic role and mechanism of MINDY2 in PC, suggesting that MINDY2 is a viable candidate gene for PC and may be a therapeutic target and critical prognostic indicator

Edge states in a two-dimensional honeycomb lattice of massive magnetic skyrmions

We study the collective dynamics of a two-dimensional honeycomb lattice of magnetic skyrmions. By performing large-scale micromagnetic simulations, we find multiple chiral and non-chiral edge modes of skyrmion oscillations in the lattice. The non-chiral edge states are due to the Tamm-Shockley mechanism, while the chiral ones are topologically protected against structure defects and hold different handednesses depending on the mode frequency. To interpret the emerging multiband nature of the chiral edge states, we generalize the massless Thiele's equation by including a second-order inertial term of skyrmion mass as well as a third-order non-Newtonian gyroscopic term, which allows us to model the band structure of skrymion oscillations. Theoretical results compare well with numerical simulations. Our findings uncover the importance of high order effects in strongly coupled skyrmions and are helpful for designing novel topological devices.Comment: 6 pages,4 figures,accepted by Physical Review B as a Rapid Communicatio

Long Non-coding RNA MAFG-AS1 Promotes Cell Proliferation, Migration, and EMT by miR-3196/STRN4 in Drug-Resistant Cells of Liver Cancer

Long non-coding RNAs (lncRNAs) have been shown to participate in the development and progression of several different types of cancer. Past studies indicated that lncRNA MAFG-antisense 1 (AS1) promotes colorectal cancer. However, the role of MAFG-AS1 in hepatocellular carcinoma (HCC) remains unclear. The aim of the present study is to examine the effect of lncRNA MAFG-AS1 on drug resistance HCC. The results indicated that MAFG-AS1 is upregulated in drug-resistant cells. Further, MAFG-AS1 promotes growth and migration of HCC by upregulating STRN4 through absorbing miR-3196. Thus, LncRNA MAFA-AS1 may become a novel target to treat HCC patients

An international collaborative investigation of beginning seventh grade students' understandings of scientific inquiry : establishing a baseline

Although understandings of scientific inquiry (as opposed to conducting inquiry) are included in science education reform documents around the world, little is known about what students have learned about inquiry during their elementary school years. This is partially due to the lack of any assessment instrument to measure understandings about scientific inquiry. However, a valid and reliable assessment has recently been developed and published, Views About Scientific Inquiry (VASI; Lederman et al. [2014], Journal of Research in Science Teaching, 51, 65–83). The purpose of this large‐scale international project was to collect the first baseline data on what beginning middle school students have learned about scientific inquiry during their elementary school years. Eighteen countries/regions spanning six continents including 2,634 students participated in the study. The participating countries/regions were: Australia, Brazil, Chile, Egypt, England, Finland, France, Germany, Israel, Mainland China, New Zealand, Nigeria, South Africa, Spain, Sweden, Taiwan, Turkey, and the United States. In many countries, science is not formally taught until middle school, which is the rationale for choosing seventh grade students for this investigation. This baseline data will simultaneously provide information on what, if anything, students learn about inquiry in elementary school, as well as their beginning knowledge as they enter secondary school. It is important to note that collecting data from all of the approximately 200 countries globally was not humanly possible, and it was also not possible to collect data from every region of each country. The results overwhelmingly show that students around the world at the beginning of grade seven have very little understandings about scientific inquiry. Some countries do show reasonable understandings in certain aspects but the overall picture of understandings of scientific inquiry is not what is hoped for after completing 6 years of elementary education in any country.http://wileyonlinelibrary.com/journal/tea2020-04-01hj2020Science, Mathematics and Technology Educatio