Search

We measure the black hole mass and investigate the accretion flow around the local ($z=0.0502$) quasar PG 1119+120. Spectroscopic monitoring with Calar Alto provides H$\beta$ lags and linewidths from which we estimate a black hole mass of $\log \left(M_{\bullet}/\mathrm{M}_{\odot} \right) = 7.0$, uncertain by $\sim0.4$ dex. High cadence photometric monitoring over two years with the Las Cumbres Observatory provides lightcurves in 7 optical bands suitable for intensive continuum reverberation mapping. We identify variability on two timescales. Slower variations on a 100-day timescale exhibit excess flux and increased lag in the $u'$ band and are thus attributable to diffuse bound-free continuum emission from the broad line region. Faster variations that we attribute to accretion disc reprocessing lack a $u'$-band excess and have flux and delay spectra consistent with either $\tau \propto \lambda^{4/3}$, as expected for a temperature structure of $T(R) \propto R^{-3/4}$ for a thin accretion disc, or $\tau \propto \lambda^{2}$ expected for a slim disc. Decomposing the flux into variable (disc) and constant (host galaxy) components, we find the disc SED to be flatter than expected with $f_{\nu} \sim \rm{const}$. Modelling the SED predicts an Eddington ratio of $\lambda_{\rm Edd} > 1$, where the flat spectrum can be reproduced by a slim disc with little dust extinction or a thin disc which requires more dust extinction. While this accretion is super-Eddington, the geometry is still unclear, however a slim disc is expected due to the high radiation pressure at these accretion rates, and is entirely consistent with our observations., Comment: 23 pages, 16 figures, 10 tables. Accepted for publication in MNRAS

We compile optical and mid-infrared light curves from the time-domain surveys (i.e. CRTS, PTF, ZTF, and ASAS-SN) and Wide-field Infrared Survey Explorer (WISE) archive for a selected sample of active galactic nuclei (AGNs) with Hβ reverberation mapping (RM) measurements. We measure the time lags (and thus torus sizes) of W1 (∼3.4 $\mu$ m) and W2 (∼4.6 $\mu$ m) band light curves relative to the optical one using the MICA method. Through Hβ RM, the sample has well-measured AGN properties, therefore allowing us to reliably constrain the relations between torus sizes and AGN properties. We perform linear regressions for the relations between torus sizes and 5100 Å luminosities ($R\propto L_{5100}^{\beta }$ ) in two cases: β = 0.5 and β set free. The latter case yields β ≈ 0.37 ± 0.028 for both W1 and W2 bands, shallower than the expected value of 0.5, possibly due to the dependence of torus size on accretion rate. For β = 0.5, by combining with the previous K band RM measurements, we obtain the characteristic broad-line region (BLR) and tours sizes following RBLR:RK :RW1:RW2 = 1.0:6.2:9.2:11.2. We investigate the deviations of the W1 and W2 band observed torus sizes from the corresponding best-fitting relations (with β = 0.5) and find that they both are correlated with accretion rate. As the accretion rate increases, the torus sizes tend to be shortened compared to the anticipated sizes from the best-fitting relations, similar to the behaviour found in BLRs. Such behaviours can be explained by the self-shadowing effect of slim discs. This is further supported by ratios of the W1 and W2 band torus sizes to BLR sizes, which do not show significant correlations with AGN properties.

Supplementary Figures 1-6 from Bmi-1 Cooperates with H-Ras to Transform Human Mammary Epithelial Cells via Dysregulation of Multiple Growth-Regulatory Pathways

Supplementary Table 1, Figures 1-5 from Mel-18 Acts as a Tumor Suppressor by Repressing Bmi-1 Expression and Down-regulating Akt Activity in Breast Cancer Cells

The Bmi-1 oncogene is overexpressed in a number of malignancies including breast cancer. In addition to Bmi-1, mammalian cells also express four other polycomb group (PcG) proteins that are closely related to Bmi-1. Virtually nothing is known about the role of these PcG proteins in oncogenesis. We have recently reported that Mel-18, a Bmi-1–related PcG protein, negatively regulates Bmi-1 expression, and that its expression negatively correlates with Bmi-1 in proliferating and senescing human fibroblasts. Here, we report that the expression of Bmi-1 and Mel-18 inversely correlates in a number of breast cancer cell lines and in a significant number of breast tumor samples. Overexpression of Mel-18 results in repression of Bmi-1 and reduction of the transformed phenotype in malignant breast cancer cells. Furthermore, the repression of Bmi-1 by Mel-18 is accompanied by the reduction of Akt/protein kinase B (PKB) activity in breast cancer cells. Similarly, Bmi-1 knockdown using RNA interference approach results in down-regulation of Akt/PKB activity and reduction in transformed phenotype of MCF7 cells. Importantly, we show that overexpression of constitutively active Akt overrides tumor-suppressive effect of Mel-18 overexpression and the knockdown of Bmi-1 expression. Thus, our studies suggest that Mel-18 and Bmi-1 may regulate the Akt pathway in breast cancer cells, and that Mel-18 functions as a tumor suppressor by repressing the expression of Bmi-1 and consequently down-regulating Akt activity. [Cancer Res 2007;67(11):5083–9]

Elevated expression of Bmi-1 is associated with many cancers, including breast cancer. Here, we examined the oncogenic potential of Bmi-1 in MCF10A cells, a spontaneously immortalized, nontransformed strain of human mammary epithelial cells (HMEC). Bmi-1 overexpression alone in MCF10A cells did not result in oncogenic transformation. However, Bmi-1 co-overexpression with activated H-Ras (RasG12V) resulted in efficient transformation of MCF10A cells in vitro. Although early-passage H-Ras–expressing MCF10A cells were not transformed, late-passage H-Ras–expressing cells exhibited features of transformation in vitro. Early- and late-passage H-Ras–expressing cells also differed in levels of expression of H-Ras and Ki-67, a marker of proliferation. Subsets of early-passage H-Ras–expressing cells exhibited high Ras expression and were negative for Ki-67, whereas most late-passage H-Ras–expressing cells expressed low levels of Ras and were Ki-67 positive. Injection of late-passage H-Ras–expressing cells in severe combined immunodeficient mice formed carcinomas with leiomatous, hemangiomatous, and mast cell components; these tumors were quite distinct from those induced by late-passage cells co-overexpressing Bmi-1 and H-Ras, which formed poorly differentiated carcinomas with spindle cell features. Bmi-1 and H-Ras co-overexpression in MCF10A cells also induced features of epithelial-to-mesenchymal transition. Importantly, Bmi-1 inhibited senescence and permitted proliferation of cells expressing high levels of Ras. Examination of various growth-regulatory pathways suggested that Bmi-1 overexpression together with H-Ras promotes HMEC transformation and breast oncogenesis by deregulation of multiple growth-regulatory pathways by p16INK4a-independent mechanisms. [Cancer Res 2007;67(21):10286–95]

Unraveling the diversification mechanisms of organisms is a fundamental and important macroevolutionary question regarding the diversity, ecological niche, and morphological divergence of life. However, many studies have only explored diversification mechanisms via isolated factors. Here, based on comparative phylogenetic analysis, we performed a macroevolutionary examination of horseshoe bats (Chiroptera: Rhinolophidae:生物物种分化机制是理解生物多样性形成、物种生态位及各类表型分化的内在核心，传统研究由于各种数据及技术限制仅能从单一的生物/非生物因素入手窥探物种历史分化机制。菊头蝠属（翼手目菊头蝠科）是该目的第二大属，在漫长的演化中形成表型及生态位各异的物种，是开展物种形成机制的天然素材。该研究通过整合各方面数据运用系统发育比较学等技术对菊头蝠属的宏进化历史进程予以分析，旨在阐明菊头蝠类群的历史物种分化驱动机制，及其与多种生物/非生物因素间的相互关系。研究表明，在物种分化的早期阶段菊头蝠属物种分化速率快速增长，随后持续下降；同时早期从亚洲扩散到东南亚及非洲的扩散事件塑造了现今的菊头蝠物种分布格局。通过整合体型、回声定位和气候生态位数据至系统发育学框架探讨其与物种形成间的内在关系，我们发现表型演化趋势与物种演化趋势不同步，这暗示着可能存在其他特殊因素驱动着菊头蝠物种表型的歧化进程。随后运用祖先状态重建及对物种演化速率与表型演化速率的结构方程模型分析，发现近缘物种分布区的重叠度与其支系的物种分化速率呈正相关，暗示着物种局部区域性的竞争潜在的驱动了后续的物种形成。综上所述，现今的菊头蝠物种多样性格局及表征状态是众多因素（生物地理学、环境因素和竞争）共同作用下塑造而成，要清晰理解类群多样性形成或维持的机制须从各方面多角度予以开展。.

Full list of authors: Bao, Dong-Wei; Brotherton, Michael S.; Du, Pu; McLane, Jacob N.; Zastrocky, T. E.; Olson, Kianna A.; Fang, Feng-Na; Zhai, Shuo; Huang, Zheng-Peng; Wang, Kai; Zhao, Bi-Xuan; Li, Sha-Sha; Yang, Sen; Chen, Yong-Jie; Liu, Jun-Rong; Yao, Zhu-Heng; Peng, Yue-Chang; Guo, Wei-Jian; Songsheng, Yu-Yang; Li, Yan-Rong; Jiang, Bo-Wei; Kasper, David H.; Chick, William T.; Nguyen, My L.; Maithil, Jaya; Kobulnicky, H. A.; Dale, D. A.; Hand, Derek; Adelman, C.; Carter, Z.; Murphree, A. M.; Oeur, M.; Schonsberg, S.; Roth, T.; Winkler, Hartmut; Marziani, Paola; D'Onofrio, Mauro; Hu, Chen; Xiao, Ming; Xue, Suijian; Czerny, Bozena; Aceituno, Jesus; Ho, Luis C.; Bai, Jin-Ming; Wang, Jian-Min; MAHA Collaboration.--This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited., In this third paper of the series reporting on the reverberation mapping campaign of active galactic nuclei with asymmetric Hβ emission-line profiles, we present results for 15 Palomar–Green quasars using spectra obtained between the end of 2016–2021 May. This campaign combines long time spans with relatively high cadence. For eight objects, both the time lags obtained from the entire light curves and the measurements from individual observing seasons are provided. Reverberation mapping of nine of our targets has been attempted for the first time, while the results for six others can be compared with previous campaigns. We measure the Hβ time lags over periods of years and estimate their black hole masses. The long duration of the campaign enables us to investigate their broad-line region (BLR) geometry and kinematics for different years by using velocity-resolved lags, which demonstrate signatures of diverse BLR geometry and kinematics. The BLR geometry and kinematics of individual objects are discussed. In this sample, the BLR kinematics of Keplerian/virialized motion and inflow is more common than that of outflow. © 2022. The Author(s). Published by the American Astronomical Society., We acknowledge the support by the National Science Foundation of China through grants NSFC-12022301, -11991051, -11991054, -11873048, -11833008, by National Key R&D Program of China (grants 2016YFA0400701), by grant No. QYZDJ-SSW-SLH007 from the Key Research Program of Frontier Sciences, Chinese Academy of Sciences (CAS), by the Strategic Priority Research Program of CAS grant No.XDB23010400, and by the International Partnership Program of CAS, grant No.113111KYSB20200014. L.C.H. was supported by the National Science Foundation of China (11721303, 11991052) and the National Key R&D Program of China (2016YFA0400702). M.B. enjoyed support from the Chinese Academy of Sciences Presidents International Fellowship Initiative, grant No. 2018VMA0005. YRL acknowledges financial support from the National Natural Science Foundation of China through grant NSFC-11922304 and from the Youth Innovation Promotion Association CAS. H.C. acknowledges financial support from grant NSFC-12122305. We also acknowledge support from a University of Wyoming Science Initiative Faculty Innovation Seed grant. This work is supported by the National Science Foundation under REU grant AST 1852289. T.E.Z. acknowledges support from NSF grant 1005444I., With funding from the Spanish government through the Severo Ochoa Centre of Excellence accreditation SEV-2017-0709.

We compile a sample of 92 active galactic nuclei (AGNs) at z < 0.75 with gri photometric light curves from the archival data of the Zwicky Transient Facility and measure the accretion disk sizes via continuum reverberation mapping. We employ Monte Carlo simulation tests to assess the influences of data sampling and broad emission lines and select out the sample with adequately high sampling cadences (3 days apart in average) and minimum contaminations of broad emission lines. The interband time delays of individual AGNs are calculated using the interpolated cross-correlation function, and then these delays are fitted with a generalized accretion disk model, in which interband time delays are a power function of wavelength, black hole mass, and luminosity. A Markov Chain Monte Carlo method is adopted to determine the best parameter values. Overall the interband time delays can be fitted with the τ ∝ λ 4/3 relation as predicted from a steady-state, optically thick, geometrically thin accretion disk; however, the yielded disk size is systematically larger than expected, although the ratio of the measured to theoretical disk sizes depends on using the emissivity- or responsivity-weighted disk radius. These results are broadly consistent with previous studies, all together raising a puzzle about the “standard” accretion disk model.

We report the results of a multiyear spectroscopic and photometric monitoring campaign of two luminous quasars, PG 0923+201 and PG 1001+291, both located at the high-luminosity end of the broad-line region (BLR) size-luminosity relation with optical luminosities above 1045 erg s-1. PG 0923+201 is monitored for the first time, while PG 1001+291 was previously monitored but our campaign has a much longer temporal baseline. We detect time lags of variations of the broad Hβ, Hγ, and Fe ii lines with respect to those of the 5100 Å continuum. The velocity-resolved delay map of Hβ in PG 0923+201 indicates a complicated structure with a mix of Keplerian disk-like motion and outflow, and the map of Hβ in PG 1001+291 shows a signature of Keplerian disk-like motion. Assuming a virial factor of f BLR = 1 and FWHM line widths, we measure the black hole mass to be for PG 0923+201 and for PG 1001+291. Their respective accretion rates are estimated to be and, indicating that PG 0923+201 is a sub-Eddington accretor and PG 1001+291 is a super-Eddington accretor. While the Hβ time lag of PG 0923+201 agrees with the size-luminosity relation, the time lag of PG 1001+291 shows a significant deviation, confirming that in high-luminosity active galactic nuclei (AGNs), the BLR size depends on both luminosity and Eddington ratio. Black hole mass estimates from single-AGN spectra will be overestimated at high luminosities and redshifts if this effect is not taken into account. © 2021. The American Astronomical Society. All rights reserved., This work is supported by the National Key R&D Program of China (2016YFA0400701, 2016YFA0400702), by the National Science Foundation of China (NSFC-11721303, 11773029, 11833008, 11873048, 11922304, 11973029, 11991051, 11991052, 11991053, 11991054, 12003036, 12022301), by the Key Research Program of Frontier Sciences of the Chinese Academy of Sciences (CAS; YZDJ-SSW-SLH007), by the CAS Key Research Program (KJZDEW-M06), by the CAS International Partnership Program (113111KYSB20200014), and by the Strategic Priority Research Program of the CAS (XDB23000000, XDB23010400). We acknowledge the support of the staff of the Lijiang 2.4 m telescope. Funding for the telescope has been provided by the CAS and the People's Government of Yunnan Province. We also acknowledge the support of the staff of the CAHA 2.2 m telescope. Y.-R.L. acknowledges financial support from the Youth Innovation Promotion Association CAS. K.H. acknowledges support from STFC grant ST/R000824/1. Based on observations obtained with the Samuel Oschin Telescope 48 inch and the 60 inch Telescope at the Palomar Observatory as part of the Zwicky Transient Facility project. ZTF is supported by the National Science Foundation and a collaboration including Caltech, IPAC, the Weizmann Institute for Science, the Oskar Klein Center at Stockholm University, the University of Maryland, Deutsches Elektronen-Synchrotron and Humboldt University, Lawrence Livermore National Laboratory, the TANGO Consortium of Taiwan, the University of Wisconsin at Milwaukee, Trinity College Dublin, and Institut national de physique nucleaire et de physique des particules. Operations are conducted by COO, IPAC, and University of Washington. This research has made use of the NASA/IPAC Extragalactic Database (NED), which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration., With funding from the Spanish government through the Severo Ochoa Centre of Excellence accreditation SEV-2017-0709.

Rituximab/chemotherapy relapsed and refractory B cell lymphoma patients have a poor overall prognosis, and it is urgent to develop novel drugs for improving the therapy outcomes. Here, we examined the therapeutic effects of chidamide, a new histone deacetylase (HDAC) inhibitor, on the cell and mouse models of rituximab/chemotherapy resistant B-cell lymphoma. In Raji-4RH/RL-4RH cells, the rituximab/chemotherapy resistant B-cell lymphoma cell lines (RRCL), chidamide treatment induced growth inhibition and G0/G1 cell cycle arrest. The primary B-cell lymphoma cells from Rituximab/chemotherapy relapsed patients were sensitive to chidamide. Interestingly, chidamide triggered the cell death with the activation of autophagy in RRCLs, likely due to the lack of the pro-apoptotic proteins. Based on the RNA-seq and chromatin immunoprecipitation (ChIP) analysis, we identified BTG1 and FOXO1 as chidamide target genes, which control the autophagy and the cell cycle, respectively. Moreover, the combination of chidamide with the chemotherapy drug cisplatin increased growth inhibition on the RRCL in a synergistic manner, and significantly reduced the tumor burden of a mouse lymphoma model established with engraftment of RRCL. Taken together, these results provide a theoretic and mechanistic basis for further evaluation of the chidamide-based treatment in rituximab/chemotherapy relapsed and refractory B-cell lymphoma patients.

Chromosomal translocation resulting in the fusion between the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene has been considered as a novel oncogenic fusion in a subset of non-small cell lung cancer (NSCLC), mostly in non-smokers with adenocarcinoma. EML4-ALK translocations are commonly reported to be mutually exclusive with epidermal growth factor receptor (EGFR) or KRAS mutations. Herein, we reported a rare case of 47-year-old female was diagnosed with lung adenocarcinoma and treated with three cycles of chemotherapy. A biopsy acquired after disease progression revealed concurrent KRAS mutation and ALK translocation by an next-generation sequencing (NGS) assay. The patient had a favorable tumor response to crizotinib, a tyrosine kinase inhibitor (TKI). A further understanding of the molecular biology with multiple oncogenic drivers will promote the optimal treatment for NSCLC.

Full list of authors: Kara, Erin; Mehdipour, Missagh; Kriss, Gerard A.; Cackett, Edward M.; Arav, Nahum; Barth, Aaron J.; Byun, Doyee; Brotherton, Michael S.; De Rosa, Gisella; Gelbord, Jonathan; Hernández Santisteban, Juan V.; Hu, Chen; Kaastra, Jelle; Landt, Hermine; Li, Yan-Rong; Miller, Jake A. ; Montano, John; Partington, Ethan; Aceituno, Jesús; Bai, Jin-Ming; Bao, Dongwei; Bentz, Misty C.; Brink, Thomas G.; Chelouche, Doron; Chen, Yong-Jie; Colmenero, Encarni Romero; Dalla Bontà, Elena; Dehghanian, Maryam; Du, Pu; Edelson, Rick; Ferland, Gary J.; Ferrarese, Laura; Fian, Carina; Filippenko, Alexei V.; Fischer, Travis; Goad, Michael R.; González Buitrago, Diego H.; Gorjian, Varoujan; Grier, Catherine J.; Guo, Wei-Jian; Hall, Patrick B.; Ho, Luis C.; Homayouni, Y.; Horne, Keith; Ilić, Dragana; Jiang, Bo-Wei; Joner, Michael D.; Kaspi, Shai; Kochanek, Christopher S.; Korista, Kirk T.; Kynoch, Daniel; Li, Sha-Sha; Liu, Jun-Rong; McHardy, Ian M.; McLane, Jacob N.; Mitchell, Jake A. J.; Netzer, Hagai; Olson, Kianna A.; Pogge, Richard W.; Popović, Luka Č.; Proga, Daniel; Storchi-Bergmann, Thaisa; Strasburger, Erika; Treu, Tommaso; Vestergaard, Marianne; Wang, Jian-Min; Ward, Martin J.; Waters, Tim; Williams, Peter R.; Yang, Sen; Yao, Zhu-Heng; Zastrocky, Theodora E.; Zhai, Shuo; Zu, Ying, We present the first results from the ongoing, intensive, multiwavelength monitoring program of the luminous Seyfert 1 galaxy Mrk 817. While this active galactic nucleus was, in part, selected for its historically unobscured nature, we discovered that the X-ray spectrum is highly absorbed, and there are new blueshifted, broad, and narrow UV absorption lines, which suggest that a dust-free, ionized obscurer located at the inner broad-line region partially covers the central source. Despite the obscuration, we measure UV and optical continuum reverberation lags consistent with a centrally illuminated Shakura-Sunyaev thin accretion disk, and measure reverberation lags associated with the optical broad-line region, as expected. However, in the first 55 days of the campaign, when the obscuration was becoming most extreme, we observe a de-coupling of the UV continuum and the UV broad emission-line variability. The correlation recovered in the next 42 days of the campaign, as Mrk 817 entered a less obscured state. The short C iv and Lyα lags suggest that the accretion disk extends beyond the UV broad-line region. © 2021. The American Astronomical Society. All rights reserved., E.K. acknowledges support from NASA grant GO1-22116X. E.M.C. and J.A.M. gratefully acknowledge support from NSF grant AST-1909199. Research at UC Irvine was supported by NSF grant AST-1907290. H.L. acknowledges a Daphne Jackson Fellowship sponsored by the Science and Technology Facilities Council (STFC), UK. J.A.J.M. and M.J.W. acknowledge support from STFC grants ST/P000541/1 and ST/T000244/1. G.J.F. and M.D. acknowledge support by NSF (1816537, 1910687), NASA (ATP 17-ATP17-0141, 19-ATP19-0188), and STScI (HST-AR- 15018 and HST-GO-16196.003-A). Y.H. acknowledges support from NASA grants HST-GO-15650 and HST-GO-16-196. D.I. and L.Č. P. acknowledge funding provided by the Astronomical Observatory Belgrade (the contract 451-03-68/2020-14/200002), University of Belgrade—Faculty of Mathematics (the contract 451-03-9/2021-14/200104) through the grants by the Ministry of Education, Science, and Technological Development of the Republic of Serbia. D.I. acknowledges the support of the Alexander von Humboldt Foundation. M.V. gratefully acknowledges financial support from the Independent Research Fund Denmark via grant No. DFF 8021-00130. J.M.W. acknowledges financial support by the National Science Foundation of China (NSFC) through grants NSFC-11833008 and -11991054. P.D. acknowledges financial support from NSFC grants NSFC-12022301, -11873048, and -11991051, and from the Strategic Priority Research Program of the CAS (XDB23010400). C.H. acknowledges financial support from the grant NSFC-11773029 and from the National Key R&D Program of China (2016YFA0400701). Y.R.L. acknowledges financial support from the grant NSFC-11922304 and from the Youth Innovation Promotion Association CAS. J.V.H.S. and K.H. acknowledge support from STFC grant ST/R000824/1. P.B.H. is supported by NSERC. Support for A.V.F.'s group at U.C. Berkeley is provided by the TABASGO Foundation, the Christopher R. Redlich Fund, and the Miller Institute for Basic Research in Science (A.V.F. is a Senior Miller Fellow). M.C.B. gratefully acknowledges support from the NSF through grant AST-2009230. D.K. acknowledges support from the Czech Science Foundation project No. 19-05599Y. L.C.H. was supported by the National Key R&D Program of China (2016YFA0400702) and the National Science Foundation of China (11721303, 11991052). J.G. gratefully acknowledges support from NASA under the ADAP award 80NSSC17K0126., With funding from the Spanish government through the Severo Ochoa Centre of Excellence accreditation SEV-2017-0709.

We report a case of concomitant EML4‐ALK and TPM3‐ROS1 fusion in non‐small cell lung cancer (NSCLC) in a 47‐year‐old Chinese man and review the clinical characteristics of this type double of fusion. The patient presented with a local tumor of the left upper lobe and underwent thoracoscopy. Postoperative surgical pathologic staging revealed T1aN0M0 stage IA. Histological examination of the tumor showed lung adenocarcinoma. Ventana ALK (D5F3) assay of the left lung tissue was ALK negative; however, immunohistochemical assay was positive for ROS1 protein. Using next generation sequencing, we found that the tumor had concomitant EML4‐ALK and TPM3‐ROS1 fusion. No recurrence was observed during seven months of follow‐up. Precise diagnostic techniques allow the detection of concomitant ROS1 fusion and other driver genes, including ALK or EGFR; therefore oncologists should consider this rare double mutation in NSCLC patients. Further exploration of treatment models is required to provide additional therapeutic options.

Gastric cancer (GC) is a serious health problem worldwide. The potential involvement of long noncoding RNAs in GC progression remains largely unexplored. Here, we identified a novel long noncoding RNA referred to as onclncRNA-626 (oncogenic lncRNA RP11-626H12.3), which was highly upregulated in GC tissues. The high expression levels of onclncRNA-626 in GC patients predicted poor prognoses. Functional assays indicated that onclncRNA-626 could promote the proliferation and metastasis of GC cells in vitro and in vivo. In exploring the molecular mechanisms guiding these functions, we found that onclncRNA-626 specifically interacted with serine- and arginine-rich splicing factor 1 (SRSF1) and increased its stability. SRSF1 was upregulated in GC tissues and correlated with onclncRNA-626 expression and patient survival. Furthermore, RNA-seq data revealed that onclncRNA-626 affected multiple signaling pathways, including the p53 signaling pathway. Rescue experiments showed that onclncRNA-626 probably performed its biological function through SRSF1 mediation of the p53 pathway. Together, our findings demonstrate that onclncRNA-626 promotes GC progression by binding SRSF1; further, this lncRNA is a potential prognostic biomarker for GC patients.

Authors: Hu, Chen; Li, Sha-Sha; Guo, Wei-Jian; Yang, Sen; Yang, Zi-Xu; Bao, Dong-Wei; Jiang, Bo-Wei; Du, Pu; Li, Yan-Rong; Xiao, Ming; Songsheng, Yu-Yang; Yu, Zhe; Bai, Jin-Ming; Ho, Luis C.; Bian, Wei-Hao; Brotherton, Michael S.; Yuan, Ye-Fei; Aceituno, Jesús; Winkler, Hartmut; Wang, Jian-Min; SEAMBH Collaboration, We report on the results of a new spectroscopic monitoring campaign of the quasar PG 0026+129 at the Calar Alto Observatory 2.2 m telescope from 2017 July to 2020 February. Significant variations in the fluxes of the continuum and broad emission lines, including Hβ and He ii, were observed in the first and third years, and clear time lags between them are measured. The broad Hβ line profile consists of two Gaussian components: an intermediate-width H with an FWHM of 1964 ± 18 and another very broad H with an FWHM of 7570 ± 83 . H has long time lags of ∼40-60 days in the rest frame, while H shows nearly zero time delay with respect to the optical continuum at 5100 Å. The velocity-resolved delays show consistent results: lags of ∼30-50 days at the core of the broad Hβ line and roughly zero lags at the wings. H has a redshift of ∼400 , which seems to be stable for nearly 30 yr by comparing with archived spectra, and may originate from an infall. The rms spectrum of H shows a double-peaked profile with brighter blue peak and extended red wing in the first year, which matches the signature of a thin disk. Both the double-peaked profile and the near-zero lag suggest that H comes from a region associated with the part of the accretion disk that emits the optical continuum. Adopting the FWHM (in the rms spectrum) and the time lag measured for the total Hβ line, and a virial factor of 1.5, we obtain a virial mass of for the central black hole in this quasar. © 2020. The American Astronomical Society. All rights reserved.., We acknowledge the support of the staff of the CAHA 2.2 m telescope. This work is based on observations collected at the Centro Astronomico Hispanoen Andalucia (CAHA) at Calar Alto, operated jointly by the Andalusian Universities and the Instituto de Astrofisica de Andalucia (CSIC). This research is supported by the National Key R&D Program of China (2016YFA0400701, 2016YFA0400702), by the National Science Foundation of China (11721303, 11773029, 11833008, 11873048, 11922304, 11973029, 11991051, 11991052, 11991054, 12003036, 12022301), by the Key Research Program of Frontier Sciences of the Chinese Academy of Sciences (CAS; QYZDJ-SSW-SLH007), by the CAS Key Research Program (KJZDEW-M06), and by the Strategic Priority Research Program of the CAS (XDB23000000, XDB23010400). J.A. acknowledges financial support from the State Agency for Research of the Spanish MCIU through the "Center of Excellence Severo Ochoa" award to the Instituto de Astrofisica de Andalucia (SEV-2017-0709).

// Zu-Guang Xia 1, * , Hua-Fang Yin 2, * , Ying Long 3, * , Lei Cheng 1 , Ling-Jun Yu 4 , Wei-Jian Guo 1 , Xiao-Dong Zhu 1 , Jin Li 1 , Ya-Nong Wang 5 , Ya-Jun Yang 6, 7 , Jiu-Cun Wang 6, 7 , Li Jin 6, 7 , Li-Xin Qiu 1 , Yongyue Wei 8 1 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China 2 Department of Medical Oncology, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangsu, China 3 Department of Medical Oncology, Wanzai City Hospital, Jiangxi, China 4 Department of Informatics, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China 5 Department of Gastric Cancer & Soft Tissue Sarcoma Surgery, Fudan University Shanghai Cancer Center, Shanghai, China 6 Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China 7 Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China 8 Department of Biostatistics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China * These authors have contributed equally to this work Correspondence to: Li-Xin Qiu, email: mdqiulixin@hotmail.com Yongyue Wei, email: ywei@njmu.edu.cn Keywords: gastric cancer, genetic susceptibility, miR-146a, polymorphism Received: January 30, 2016 Accepted: March 31, 2016 Published: April 18, 2016 ABSTRACT The single nucleotide polymorphism (SNP) rs2910164 G>C within miR-146a has been reported that is associated with the increased risk of gastric cancer (GCa). However, the results are inconclusive, espicially among Asian populations, which probably due to small sample size in each single study. To validate this association and get a more precise estimation, we conducted a large GCa study including 1,125 cases and 1,196 controls in an eastern Chinese population. Our results showed that this SNP was not associated with GCa risk in either of the three genetic models [co-dominant model: CG vs. CC, odds ratio (OR) = 0.99, 95% confidence interval (95%CI): 0.83-1.19; GG vs. CC, OR = 1.03, 95%CI: 0.81-1.32; dominant model: (CG+GG) vs. CC, OR = 1.00, 95%CI = 0.84-1.19; recessive model: GG vs. (CG+CC), OR = 1.04, 95%CI = 0.83-1.29]. Stratified analysis by age, gender, smoking status, drinking status, or tumor location confirmed this non-significant association. In summary, these results suggest that the miR-146a SNP rs2910164 may not be a risk factor for GCa in this Chinese population. Larger and well-designed, preferably prospective studies are needed to further confirm our findings.

Published data on the association between the MUC1 rs4072037A > G polymorphism and gastric cancer (GCa) risk were inconclusive. To derive a more precise estimation of the association, we conducted a large GCa study of 1,124 cases and 1,192 controls to confirm this association in an Eastern Chinese population. Our results showed that the G allele was strongly associated with a decreased GCa risk in the study population [GG vs. AA, odds ratio (OR) = 0.47, 95% confidence interval (CI) = 0.31–0.73; AG/GG vs. AA, OR = 0.82, 95% CI = 0.68–0.99; GG vs. AA/AG, OR = 0.48, 95% CI = 0.32–0.74]. These associations remained significant in subgroups of age, tumor site, drinking and smoking status. Moreover, this association was supported by an additional meta-analysis of published studies. In summary, these results suggest that the MUC1 rs4072037G allele may be a low-penetrating protection factor for GCa risk in Chinese populations.

The prostate stem cell antigen (PSCA) gene, which encodes a prostate-specific antigen (PSA), was identified as a gene involved in cell adhesion and proliferation. The associations between the PSCA rs2294008 and rs2976392 single nucleotide polymorphisms (SNPs) and gastric cancer (GCa) susceptibility were still controversial. To derive a more precise estimation of the associations, we conducted a case-control study of 1,124 cases and 1,192 controls in an eastern Chinese population. We found that the rs2294008T variant genotypes were associated with an increased GCa risk in this study population (CT vs CC, OR=1.59, 95% CI=1.33-1.89 and CT+TT vs CC, OR=1.38, 95% CI=1.17-1.62). For SNP rs2976392, the variant A genotypes were also associated with an increased GCa risk (AG vs GG, OR=1.61, 95% CI=1.35-1.91 and AG+AA vs GG, OR=1.47, 95% CI=1.25-1.74). The results were further validated by a meta-analysis. In conclusion, the results indicated that the PSCA rs2294008 T and rs2976392 A alleles were low-penetrate risk factors for GCa in this study population. However, large and well-designed studies are warranted to validate our findings.

// Li-Xin Qiu 1, 2, * , Jing He 3, * , Lei Cheng 2, * , Fei Zhou 2 , Meng-Yun Wang 2 , Meng-Hong Sun 4 , Xiao-Yan Zhou 4 , Jin Li 1 , Wei-Jian Guo 1 , Ya-Nong Wang 5 , Ya-Jun Yang 6, 7 , Jiu-Cun Wang 6, 7 , Li Jin 6, 7 , Xiao-Dong Zhu 1 , Qing-Yi Wei 2, 8 1 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China 2 Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China 3 Department of Pediatric Surgery, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China 4 Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China 5 Department of Gastric Cancer and Soft Tissue Sarcoma Surgery, Fudan University Shanghai Cancer Center, Shanghai, China 6 Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China 7 Fudan-Taizhou Institute of Health Sciences, Jiangsu, China 8 Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA * These authors have contributed equally to this work Correspondence to: Xiao-Dong Zhu, e-mail: xddr@netease.com Qing-Yi Wei, e-mail: weiqingyi@yahoo.com and Qingyi.wei@duke.edu Keywords: PRKA71, polymorphism, gastric cancer, genetic susceptibility Received: August 04, 2015 Accepted: October 09, 2015 Published: October 15, 2015 ABSTRACT Published data on the association between PRKAA1 rs13361707 T > C polymorphism and gastric cancer (GCa) susceptibility were inconclusive. To derive a more precise estimation of the association, we conducted a large-scale GCa study of 1,124 cases and 1,194 controls to confirm this association in an eastern Chinese population. Our results showed that the C allele of PRKAA1 rs13361707 increased the GC risk in the study population [CT vs. TT, odds ratio (OR) = 1.72, 95% confidence interval (CI) = 1.40–2.12; CC vs. TT, OR = 2.15, 95%CI = 1.70–2.71; CT/CC vs. TT, OR = 1.86, 95%CI = 1.53–2.26; CC vs.TT/CT, OR = 1.49, 95%CI = 1.24–1.79]. In addition, the association of C allele with an increased GCa risk was still significant in subgroups, when stratified by age, sex, tumor site, drinking and smoking status. Moreover, the findings in the present study were validated by our further meta-analysis. In summary, these results indicated that the C allele of PRKAA1 rs13361707 was a low-penetrate risk factor for GCa.

The tumour suppressor p53 plays an important role in tumourigenesis. Besides inducing apoptosis, it regulates cellular senescence, which constitutes an important barrier to tumourigenesis. The mechanism of regulation of cellular senescence by p53 and its downstream pathway are poorly understood. Here, we report that the ubiquitin domain-containing 1 (UBTD1) gene, a new downstream target of p53, induces cellular senescence and acts as a novel tumour suppressor by a mechanism that depends on p53. Expression of UBTD1 increased upon cellular senescence induced by serial passageing of cultures, as well as by exposure to DNA-damageing drugs that induce premature senescence. Over-expression of UBTD1 induces senescence in human fibroblasts and cancer cells and attenuation of the transformed phenotype in cancer cells. UBTD1 is down-regulated in gastric and colorectal cancer tissues, and its lower expression correlates with a more aggressive phenotype and worse prognosis. Multivariate analysis revealed that UBTD1 expression was an independent prognostic factor for gastric cancer patients. Furthermore, UBTD1 increased the stability of p53 protein, by promoting the degradation of Mdm2 protein. Importantly, UBTD1 and p53 function mutually depend on each other in regulating cellular senescence and proliferation. Thus, our data suggest that, upon DNA damage, p53 induction by UBTD1 creates a positive feedback mechanism to further increase p53 expression. Our results establish UBTD1 as a regulator of cellular senescence that mediates p53 function, and provide insights into the mechanism of Mdm2 inhibition that impacts p53 dynamics during cellular senescence and tumourigenesis. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The universal tool microscope is widely applied in geometric measurement, as the imaging method is a typical measurement methods. In this paper, data processing and calculation example to specify the method of image measurement of the external thread, Classifications have been carried out systematically in this paper on the origin of error of the universal tool microscope, the image- measuring methods was summarized.

PURPOSE : Treatment effects of advanced gastric cancer (AGC) are unsatisfactory, and novel therapeutic approaches are much needed. The epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab inhibits the growth of several human cancer cells but has been tested rarely for the treatment of GC. The synergy between cetuximab and irinotecan has been reported in colorectal cancer, but the mechanisms are still not fully clarified. Consequently, we hypothesized cetuximab/irinotecan combination should enhance the antitumor activity of irinotecan in GC cells. METHODS : The in vitro antiproliferative, pro-apoptotic, cell cycle arrest effects and induction of senescence were examined in SGC-7901 and MKN-45 GC cell lines. The effects of cetuximab or irinotecan as single agents or the combination on the expression of p53, p16, and EGFR signaling pathways were also studied. RESULTS : The study revealed that cetuximab alone did not show any antiproliferative, pro-apoptotic, cell cycle arrest or cellular senescence effect on GC cells but when combined with irinotecan synergistically inhibits GC cell proliferation and induces apoptosis and G2/M phase arrest. Irinotecan increases phosphorylation of EGFR, MAPK, and AKT and decreases the expression of P27(Kip1), which could be all abrogated by its combination with cetuximab. The combination could also inhibit the expression of Cyclin D1 and phosphorylated mTOR while had no impact on p53, p16, PTEN, and HIF-1alpha. CONCLUSIONS : Cetuximab enhances the activities of irinotecan on GC cells via the downregulation of the EGFR pathway upregulated by irinotecan. Combination therapy with cetuximab and irinotecan, a novel therapeutic approach, warrants further study in GC.

Elevated expression of Bmi-1 is associated with many cancers, including breast cancer. Here, we examined the oncogenic potential of Bmi-1 in MCF10A cells, a spontaneously immortalized, nontransformed strain of human mammary epithelial cells (HMEC). Bmi-1 overexpression alone in MCF10A cells did not result in oncogenic transformation. However, Bmi-1 co-overexpression with activated H-Ras (RasG12V) resulted in efficient transformation of MCF10A cells in vitro. Although early-passage H-Ras–expressing MCF10A cells were not transformed, late-passage H-Ras–expressing cells exhibited features of transformation in vitro. Early- and late-passage H-Ras–expressing cells also differed in levels of expression of H-Ras and Ki-67, a marker of proliferation. Subsets of early-passage H-Ras–expressing cells exhibited high Ras expression and were negative for Ki-67, whereas most late-passage H-Ras–expressing cells expressed low levels of Ras and were Ki-67 positive. Injection of late-passage H-Ras–expressing cells in severe combined immunodeficient mice formed carcinomas with leiomatous, hemangiomatous, and mast cell components; these tumors were quite distinct from those induced by late-passage cells co-overexpressing Bmi-1 and H-Ras, which formed poorly differentiated carcinomas with spindle cell features. Bmi-1 and H-Ras co-overexpression in MCF10A cells also induced features of epithelial-to-mesenchymal transition. Importantly, Bmi-1 inhibited senescence and permitted proliferation of cells expressing high levels of Ras. Examination of various growth-regulatory pathways suggested that Bmi-1 overexpression together with H-Ras promotes HMEC transformation and breast oncogenesis by deregulation of multiple growth-regulatory pathways by p16INK4a-independent mechanisms. [Cancer Res 2007;67(21):10286–95]