The epithelial-mesenchymal transition (EMT) is the pivotal mechanism underlying the initiation of cancer invasion and metastasis. Although Mel-18 has been implicated in several biological processes ...in cancer, its function in the EMT of human cancers has not yet been studied. Here, we demonstrate that Mel-18 negatively regulates the EMT by epigenetically modulating miR-205. We identified miR-205 as a novel target of Mel-18 using a microRNA microarray analysis and found that Mel-18 increased miR-205 transcription by the inhibition of DNA methyltransferase-mediated DNA methylation of the miR-205 promoter, thereby downregulating its target genes, ZEB1 and ZEB2. Furthermore, the loss of Mel-18 promoted ZEB1- and ZEB2-mediated downregulation of E-cadherin transcription and also enhanced the expression of mesenchymal markers, leading to increased migration and invasion in MCF-7 cells. In MDA-MB-231 cells, Mel-18 overexpression restored E-cadherin expression, resulting in reduced migration and invasion. These effects were reversed by miR-205 overexpression or inhibition. A tumor xenograft with Mel-18 knockdown MCF-7 cells consistently showed increased ZEB1 and ZEB2 expression and decreased E-cadherin expression. Taken together, these results suggest that Mel-18 functions as a tumor suppressor by its novel negative control of the EMT, achieved through regulating the expression of miR-205 and its target genes, ZEB1 and ZEB2.
This study aimed to detect signals of adverse drug reactions (ADRs) associated with biological disease-modifying antirheumatic drugs (DMARDs) and targeted therapies in rheumatoid arthritis (RA) and ...ankylosing spondylitis (AS) patients. Utilizing the KOrean College of Rheumatology BIOlogics & Targeted Therapy Registry (KOBIO) data, we calculated relative risks, excluded previously reported drug-ADR pairs, and externally validated remaining pairs using US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and single centre's electronic health records (EHR) data. Analyzing data from 2279 RA and 1940 AS patients, we identified 35 significant drug-ADR pairs in RA and 26 in AS, previously unreported in drug labels. Among the novel drug-ADR pairs from KOBIO, 15 were also significant in the FAERS data. Additionally, 2 significant drug-laboratory abnormality pairs were found in RA using CDM MetaLAB analysis. Our findings contribute to the identification of 14 novel drug-ADR signals, expanding our understanding of potential adverse effects related to biological DMARDs and targeted therapies in RA and AS. These results emphasize the importance of ongoing pharmacovigilance for patient safety and optimal therapeutic interventions.
Highlights • We expressed a recombinant major capsid protein (rMCP) of rock bream iridovirus in rice callus. • Fish immunized orally with rMCP underwent successful induction of antibodies and were ...protected against viral challenge. • Transgenic single-cell cultures offer advantages over whole-plant systems with high level containment. • Plant-based oral administration protocol could be used as an effective (less labor and stress) means of accomplishing practical vaccine trials.
Gene fusion is involved in the development of various types of malignancies. Recent advances in sequencing technology have facilitated identification of gene fusions and have stimulated the research ...of this field in cancer. In the present study, we performed next-generation transcriptome sequencing in order to discover novel gene fusions in gastric cancer. A total of 282 fusion transcript candidates were detected from 12 gastric cancer cell lines by bioinformatic filtering. Among the candidates, we have validated 19 fusion transcripts, which are 7 inter-chromosomal and 12 intra-chromosomal fusions. A novel DUS4L-BCAP29 fusion transcript was found in 2 out of 12 cell lines and 10 out of 13 gastric cancer tissues. Knockdown of DUS4L-BCAP29 transcript using siRNA inhibited cell proliferation. Soft agar assay further confirmed that this novel fusion transcript has tumorigenic potential. We also identified that microRNA-coding gene PVT1, which is amplified in double minute chromosomes in SNU-16 cells, is recurrently involved in gene fusion. PVT1 produced six different fusion transcripts involving four different genes as fusion partners. Our findings provide better insight into transcriptional and genetic alterations of gastric cancer: namely, the tumorigenic effects of transcriptional read-through and a candidate region for genetic instability.
•We assessed the goodness-of-fit of different distributions to wind speed data in the UAE.•Performances of parametric, mixture and non-parametric distributions are compared.•Mixture of two-component ...Weibull distribution gives the overall best fit.•The Kappa and Generalized Gamma are the parametric distributions giving the best fit.
For the evaluation of wind energy potential, probability density functions (pdfs) are usually used to describe wind speed distributions. The selection of the appropriate pdf reduces the wind power estimation error. The most widely used pdf for wind energy applications is the 2-parameter Weibull probability density function. In this study, a selection of pdfs are used to model hourly wind speed data recorded at 9 stations in the United Arab Emirates (UAE). Models used include parametric models, mixture models and one non-parametric model using the kernel density concept. A detailed comparison between these three approaches is carried out in the present work. The suitability of a distribution to fit the wind speed data is evaluated based on the log-likelihood, the coefficient of determination R2, the Chi-square statistic and the Kolmogorov–Smirnov statistic. Results indicate that, among the one-component parametric distributions, the Kappa and Generalized Gamma distributions provide generally the best fit to the wind speed data at all heights and for all stations. The Weibull was identified as the best 2-parameter distribution and performs better than some 3-parameter distributions such as the Generalized Extreme Value and 3-parameter Lognormal. For stations presenting a bimodal wind speed regime, mixture models or non-parametric models were found to be necessary to model adequately wind speeds. The two-component mixture distributions give a very good fit and are generally superior to non-parametric distributions.
The Kondo insulator SmB6 has long been known to exhibit low-temperature transport anomalies whose origin is of great interest. Here we uniquely access the surface electronic structure of the ...anomalous transport regime by combining state-of-the-art laser and synchrotron-based angle-resolved photoemission techniques. We observe clear in-gap states (up to ~4 meV), whose temperature dependence is contingent on the Kondo gap formation. In addition, our observed in-gap Fermi surface oddness tied with the Kramers' point topology, their coexistence with the two-dimensional transport anomaly in the Kondo hybridization regime, as well as their robustness against thermal recycling, taken together, collectively provide strong evidence for protected surface metallicity with a Fermi surface whose topology is consistent with the theoretically predicted topological Fermi surface. Our observations of systematic surface electronic structure provide the fundamental electronic parameters for the anomalous Kondo ground state of correlated electron material SmB6.
We present a comprehensive study of the nonproportionality of NaI(Tl) scintillation detectors within the context of dark matter search experiments. Our investigation, which integrates COSINE-100 data ...with supplementary
γ
spectroscopy, measures light yields across diverse energy levels from full-energy
γ
peaks produced by the decays of various isotopes. These
γ
peaks of interest were produced by decays supported by both long and short-lived isotopes. Analyzing peaks from decays supported only by short-lived isotopes presented a unique challenge due to their limited statistics and overlapping energies, which was overcome by long-term data collection and a time-dependent analysis. A key achievement is the direct measurement of the 0.87 keV light yield, resulting from the cascade following electron capture decay of
22
Na
from internal contamination. This measurement, previously accessible only indirectly, deepens our understanding of NaI(Tl) scintillator behavior in the region of interest for dark matter searches. This study holds substantial implications for background modeling and the interpretation of dark matter signals in NaI(Tl) experiments.
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.
We present new constraints on the dark matter-induced annual modulation signal using 1.7 years of COSINE-100 data with a total exposure of 97.7 kg yr. The COSINE-100 experiment, consisting of 106 kg ...of NaI(Tl) target material, is designed to carry out a model-independent test of DAMA/LIBRA's claim of WIMP discovery by searching for the same annual modulation signal using the same NaI(Tl) target. The crystal data show a 2.7 cpd/kg/keV background rate on average in the 2-6 keV energy region of interest. Using a χ-squared minimization method we observe best fit values for modulation amplitude and phase of 0.0092±0.0067 cpd/kg/keV and 127.2±45.9 d, respectively.
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