bluuebunny/crossref_metadata_2025 huggingface dataset:
Hipparcos Stars in The GCVS
Authors: Samus N.N.
Published: June 2021

Prof. M. Grenon asked the team of the General Catalogue of Variable Stars to attribute GCVS names to new Hipparcos variables in order to present, in the Hipparcos Catalogue, the information on these stars already with final designations. We received lists of 5665 variables. Of them, 3157 qualified to the standard GCVS criteria and will appear in the 74th Namelist of variable stars.

The main problems in compiling the Namelist were the following:

1.

Cases of spurious variability for double and multiple stars and for misidentified stars (wrong colour indices used in reductions). Some wrong identifications come from the SIMBAD data base.

2.

Lacking identifications with catalogues of spectroscopic binaries. Some stars attributed to slowly pulsating B variables are in fact ellipsoidal variables. HIP 98954 = V1472 Aql was classified as a semiregular star, but it is a rather unusual, probably eclipsing, star (Samus, 1997), a known spectroscopic-binary M giant with a 200d period (Lucke and Mayor, 1982).
CPC2 Reduction with Hipparcos and Proper Motions in The Southern Hemisphere
Authors: Zacharias N. , Zacharias M.I. , de Vegt C. , Murray C.A.
Published: June 2021

The Second Cape Photographic Catalog (CPC2) contains 276,131 stars covering the entire Southern Hemisphere in a 4-fold overlap pattern. Its mean epoch is 1968, which makes it a key catalog for proper motions. A new reduction of the 5687 plates using on average 40 Hipparcos stars per plate has resulted in a vastly improved catalog with a positional accuracy of about 40 mas (median value) per coordinate, which comes very close to the measuring precision. In particular, for the first time systematic errors depending on magnitude and color can be solved unambiguously and have been removed from the catalog. In combination with the Tycho Catalogue (mean epoch 1991.25) and the upcoming U.S. Naval Observatory CCD Astrograph Catalog (UCAC) project proper motions better than 2 mas/yr can be obtained. This will lead to a vastly improved reference star catalog in the Southern Hemisphere for the final Astrographic Catalogue (AC) reductions, which will then provide propermotions for millions of stars when combined with new epoch data. These data
then will allow an uncompromised reduction of the southern Schmidt surveys on the International Celestial Reference System (ICRS).
Impact of The Hipparcos Data on The Astrometric Reduction of The Outer Planets
Authors: Fienga A.
Published: June 2021

We investigated the improvement of photographic astrometric observations of outer planets by use of Hipparcos Catalogue stars. The position of Jupiter on the plates was determined from measurements of the Galilean satellites, combined with ephemerides accurate to better than 10 mas. In a 6 contants model of photographic plates reduction, when images are near the center of the field, only offsets have to be computed, by considering the scale and orientation known. We applied this idea to the galilean satellites by using137 photographic plates realised between 1967 and 1974 by D. Pascu, with the Mc Cormick 26-inch refractor, Virginia, and its twin in the USNO, Washington DC. A study of the scale factors reveals an expected anisotropy of the scale factors. One possible hypothesis is that this effect is a consequence of the thermal expansions of the telescopic components. The use of Hipparcos data in the astrometric reduction allows to obtain an external error of around 40 mas on the determination of the observed absolute position of Jupiter. It is 5 times better than the classic computations using photographic or CCD reductions. Furthemore, with such results, badly-known effects can be easly estimated like the anisotropy of scale. At the end, important impacts on the fit of planetary ephemerides to the visual observations are expected.
Rigidity Estimation of The Hipparcos System in The Equatorial Zone By 20-Th Century Ground-Based Observations
Authors: Kolesnik Y.B.
Published: June 2021

The external systematic accuracy of the HIPPARCOS positions and proper motions in the equatorial zone as represented by the subset of its bright FK5 stars is estimated by comparison with modern ground-based catalogues of 1980-1990s as well as with the most precise compiled catalogues made in the 20th century. Significant zonal and regional systematic differences between Hipparcos and ground-based catalogues have been detected for the different epochs ranging from 1920 to 1990. The most typical behaviour of the analysed differences at the epoch 1991.25 is almost absence of small-scale deviations and presence of the large-scale features. For the epoch 1920, both large and small-scale discrepancies are more pronounced reaching up to 50 mas. This gives evidence of the inferiour consistency of the HIPPARCOS system with ground-based observations comparing with the best compiled catalogues.
Earth Orientation Parameters 1899.7-1992.0 In The Hipparcos Reference Frame
Authors: Vondrák J. , Ron C. , Pešek I. , Čepek A.
Published: June 2021

The optical astrometry observations of latitude/universal time variations made with 48 instruments at 31 observatories are used to determine the Earth orientation parameters (EOP) since the beginning of the century. The Hipparcos Catalogue is used to bring more than four million individual observations, made in the interval 1899.7-1992.0, into the International Celestial Reference System. The Earth orientation parameters (polar motion, celestial pole offsets and, since 1956.0, also universal time UT1) are determined at 5-day intervals, with average uncertainties ranging from 8 mas (in the eighties) to about 40 mas (in the forties). Making use of very long series of ground-based observations, the solution also leads to the improvement of proper motions of about ten per cent of the observed Hipparcos stars, with precision of ±0.2 — 0.5 mas/yr. In addition, 474 auxiliary parameters, describing the rheological properties of the Earth and seasonal deviations of the observations at contributing observatories, are found. The new solution provides the EOP series suitable for further analyses, e.g., for studying long-periodic polar motion, length-of-day changes or precession/nutation.
The Luminosity Calibration of the HR Diagram
Authors: Gómez A.E. , Luri X. , Mennessier M.O. , Torra J. , Figueras F. , Royer F.
Published: June 2021

An extensive work on the luminosity calibration of the HR diagram has been performed using the LM method based on the Maximum Likelihood estimation (Luri et al. 1996). The method uses all available information: Hipparcos parallax and proper motion data as well as radial velocities and some measured spectroscopic or photometric parameters related to luminosity. On the other hand, the method takes into account the censorship of the sample and the errors of the data. Finally, it is able to identify and separate in a given sample, groups with different luminosity, kinematical or spatial characteristics providing not only the corresponding luminosity calibration relationship, but also improved individual absolute magnitude estimates.

In order to asses how reliable the luminosity calibrations based on the MK spectral classification are, the LM method has been applied to a sample of B to K stars with MK classification selected from the Hipparcos survey. All known binaries, variables and spectroscopically peculiar stars were removed from the sample. The final sample contains 22054 stars. Our results show that the relation between absolute magnitude and luminosity class has a large intrinsic dispersion. As a consequence, the assignation to a star of a mean absolute magnitude given by a MK classification calibration is a rough procedure. It is preferable to use the individual absolute magnitudes estimated using all the available information for each star, like the estimates provided by the LM method (Gómez et al. 1997).
Parallaxes and Proper Motions of Prototypes of Astrophysically Interesting Classes of Stars
Authors: Trimble V. , Herbig G.H. , Kundu A.
Published: June 2021

Early release data were obtained under the 1982 announcement of opportunity for about two dozen stars belonging to seven classes whose basic properties or evolutionary status were uncertain at the time. A good many remain so. Many of the stars were too faint and far for parallaxes to be statistically significant, though many of the proper motions are. Two papers presenting the data have been accepted by archival journals (Trimble and Kundu 1997, 1998). Both bear the same title as this Abstract The first deals with the R Coronae Borealis variables, the second with the other six classes (FK Comae Stars, CVs, runaway T Tauri stars, and so forth).
The Age of Old Galactic Populations
Authors: Grenon M.
Published: June 2021

As a preparation to the HIPPARCOS mission, a large observing programme on NLTT stars (propermotion > 0.18 ″/yr) was started in Genevaphotometry. The original programme consists of 10047 stars brighter than mR = 11.5, or mR = 12.5 if of colour class m. Among them, 7813 targets could be included in the HIPPARCOS programme, selected according to their observability and internal priorities in favour of large parallaxe stars (photometric distances < 100 pc) and high-velocity stars. The bulk of new nearby, halo, mild-metal poor and SMR stars in the HIP Catalogue originates from this proposal (N° 139). No less than 208 new nearby stars with π ≥ 40 mas were discovered south of δ +10°, the closest has π(HIP)= 182 mas. Radial velocities were obtained with CORAVEL at OHP and ESO. Most aspects of the early evolution of the Galaxy may be addressed with this sample. Here we discuss, as examples, the ages of the thick disk and of the galactic bulge.
Absolute Proper Motions of Bulge Giants in the Hipparcos System
Authors: Minniti D. , Lattanzi M.G. , Claria J.J. , Massone G. , Casalegno R.
Published: June 2021

Three windows towards the Galactic bulge, located at (l, b) = (1.6,-2.8), (5.2,-3.5), and (4.2,-4.8), were identified from deep astrometric plates. Deep BVRI CCD photometry of these fields reaching V = 18.5 was obtained at the ESO Dutch telescope. The color-color and color magnitude diagrams of these fields allow us to select different bulge tracers, including blue horizontal branch stars, red clump giants, and RGB tip stars, as well as disk main-sequence stars. A first catalogue of some 2000 red clump giants was constructed, and measurement of their proper motions in under way. We are deriving absolute proper motions in the Hipparcos system using a two step procedure. First, plates from the Cordoba archive of the Astrographic Catalogue (epochs 1903-1913) are used in combination with recent plates from theESO GPO telescope to tie a set of intermediate magnitude field stars in the Hipparcos system of positions and proper motions. Second, deeper intermediate epoch (1958) and final epoch CCD images (epoch 1996.5) are used to determine the absolute proper motions of the fainter bulge stars. The average uncertainty in the absolute proper motion of a single giant, based on a preliminary sample of few tens of stars, is 0”.006 yr-1. This
relatively small error, in combination with the sample size, would allow usto study the shape of the velocity ellipsoid for the different Galactic components present in the inner regions as function of Galactocentric distance, and also to measure an accurate distance to the Galactic center and the
mass of the bulge. In addition, we identified about 20 faint objects which are potential members of the Sgr dwarf, based on their location in the color-magnitude diagrams, and are also measuring their proper motions.

Other windows with measured proper motions are located along the Galactic minor axis, including Baade’s window at l, b = (1, −4) (Spaenhauer, A., Jones, B. F., &: Whitford, A. E., 1992, A3, 103, 297), and the Plaut field at l, b = (0, - 8 ) (Mendez, R. et al., 1997, in 4th ESO/CTIO Workshop on “The Galactic Center”, in press). Our proper motions are complementary, probing the kinematics off the Galactic minor axis, where the signature of rotation should be evident. The
fields chosen for this study overlap fields that the MACHO project is following since 1993. Their variable star database would provide with excellent tracers of different populations. The 3-D motions of these different Galactic components would be measured for the first time. These include RR Lyrae tracers of the inner metal-poor halo, Miras, LPVs and delta Scuti stars tracers of the metal-rich bulge, and eclipsing binaries tracers of the Galactic disk (Minniti, D., et al., 1996, in IAP Coll. on “Variable Stars and the Astrophysical Returns of Microlensing Surveys”, ed. R. Ferlet, p. 257; Alcock, C, et al., 1997, astro-ph/9707311).
Populations Among High-Velocity Early-Type Stars
Authors: Royer F. , Gómez A.E.
Published: June 2021

As far as the standard picture of galactic evolution and structure is concerned, early-type stars belong to disk populations. However, the existence of a population of early-type stars with nearsolar metallicities and main-sequence surface gravities, together with high velocities and/or standing at large distances away from the plane, is a well known anomaly to this picture.

In order to provide an insight into the different populations of early-type stars, a sample of high-velocity stars has been gathered from the Hipparcos catalogue. We have selected the stars according to B — V < 0.4,and a tangential velocity larger than 80 km/s. The sample is composed of 101 stars.

The high-velocity early-type stars in the solar neighbourhood are a mixture of different stellar populations: blue horizontal halo stars passing near the sun and high-velocity disk stars. We have decomposed into gaussiansthe V and W-distributions of our sample, to isolate the disk from the halo populations. The U-distribution of high-velocity disk stars is clearly asymmetric. The selection bias over the tangential velocities creates a depletion of low U values. Moreover, two thirds of the sample have U < 0 (toward the galactic anticentre, l = 180°). This cannot be explained by the distribution tail of disk stars or stochastic events such as runaway stars, which privilege no direction.
The Absolute Magnitude Of RR Lyrae Stars
Authors: Tsujimoto T. , Miyamoto M. , Yoshii Y.
Published: June 2021

The present determination of the absolute magnitude .Mv(RR) of RR Lyrae stars is twofold, relying upon Hipparcos proper motions and trigonometric parallaxes separately. First, applying the statistical parallax method to the proper motions, we find < Mv(RR)>= 0.69 ± 0.10 for 99 halo RR Lyraes with <[Fe/H]> = -1.58. Second, applying the Lutz-Kelker correction to the RR Lyrae HIP95497 with the most accurately measured parallax, we obtain Mv(RR) = 0.57-0.74 at [Fe/H]=-1.6. Furthermore, allowing full use of low accuracy and negative parallaxes as well for 125 RR Lyraes with - 2.49≤[Fe/H]≤0.07, the maximum likelihood estimation yields the relation, Mv(RR)= (0.59±0.37)+(0.20±0.63)([Fe/H]+1.60), which formally agrees with the recent preferred relation. The same estimation yields again My (RR) = 0.65 ± 0.33 for the 99 halo RR Lyraes. Although the formal errors in the latter two estimates are rather large, all of the four results suggest the fainter absolute magnitude, My(RR)=0.6-0.7 at [Fe/H]=-1.6. The present results still provide the lower limit on the age of the universe which is inconsistent with a fiat, matter-dominated universe and current estimates of the Hubble constant.
Suggestion to Revise the Hipparcos-Parallax of Cepheids Belonging to Binary Systems
Authors: Szabados L.
Published: June 2021

It has been suspected (Szabados 1997) that the apparent orbit of previously unresolved binaries involving a Cepheid component falsifies the Hipparcos-parallaxes deduced for these Cepheids. Since the incidence of binaries among Cepheids exceeds 50 per cent, this adverse effect on the parallax determination is a major error source.

An obvious remedy is to repeat the determination of the five astrometric parameters for the Cepheids, members in binary systems, taking into accountthe orbital elements known from spectroscopic studies. This will result in more precise parallaxes and cosmic distance scale. Moreover, these Cepheidsare ideal targets for the future microarcsec astrometric missions.

This study was partly supported by OTKA-grants T 014852 and T 022946.
Diva - A Small Satellite for Global Astrometry and Photometry
Authors: Röser S. , Bastian U. , de Boer K.S. , Høg E. , Schilbach E. , de Vegt CH. , Wagner S.
Published: June 2021

DIVA (Double Interferometer for Visual Astrometry) is a Fizeau interferometer on a small satellite. It will perform astrometric and photometric observations of at least 4 million stars. A launch in 2002 and a minimum mission length of 24 months are aimed at. A detailed description of the experiment can be obtained from the DIVA homepage at http://www.aip.de:8080/dso/diva. An overview is given by Röser et al., 1997.

The limiting magnitude of DIVA is about V = 15 for spectral types earlier than M0, but drops to about V = 17.5 for stars later than M5. Table 1 gives a short overview on DIVA’s performance. DIVA will carry out a skysurvey complete to V = 12.5. For the first time this survey will comprise precise photometry in at least 8 bands in the wavelength range from 400 to 1000 nm.

DIVA will improve parallaxes by a factor of 3 compared to Hipparcos; proper motions by at least a factor of 2 and, in combination with the Hipparcos observations, by a factor of 10 for Hipparcos stars. At least 30 times asmany stars as Hipparcos will be observed, and doing this DIVA will fill the gap in observations between Hipparcos and GAIA. DIVA’s combined astrometric and photometric measurements of high precision will have important impacts on astronomy and astrophysics in the next decade.
The Instrument of the Astrometric Mission Diva
Authors: Wagner S.J. , Seifert W. , Mandel H. , Bastian U. , RÖser S.
Published: June 2021

As a follow-up to the most successful Hipparcos mission we have suggested a mini-satellite. The instrument DIVA is a pair of two small Fizeau interferometers with a fixed angular separation scanning the entire sky in a Hipparcos-type fashion. Despite its small apertures the very efficient opticaldesign and the use of CCD detectors will allow a significant increase in performance compared to the Hipparcos mission. Introducing objective prisms in front of the beam combiners will generate dispersed fringes which will allow a more accurate astrometry and much more detailed spectro-photometric information than filtered, undispered fringes. A complete optical system was
designed which is suitable to achieve the desired goal and may be expanded to the size of GAIA. Likewise, several options exists to improve the capabilities and the depth of the DIVA mission.
Exploring the Impact of Cenomanian Paleogeography and Marine Gateways on Oceanic Oxygen
Authors: Laugié Marie , Donnadieu Yannick , Ladant Jean‐Baptiste , Bopp Laurent , Ethé Christian , Raisson François
Published: June 2021

The Cenomanian‐Turonian period recorded one of the largest disruptions to the oxygen and carbon cycles, the Oceanic Anoxic Event 2 (OAE2, 94 Ma). This event is global, yet paleo‐reconstructions document heterogeneous ocean oxygenation states and sedimentary carbon contents, temporally and spatially, suggesting that several mechanisms are at play. To better understand the long‐term controls on oceanic oxygen and the initial oxygenation conditions prevailing at the beginning of OAE2, we perform numerical simulations of the Cenomanian using the IPSCL‐CM5A2 Earth System Model, which includes a marine biogeochemistry component. We examine the control of the biogeochemical states of the global and Central Atlantic oceans by the depth of the Central American Seaway (CAS). The simulations show that a vigorous ocean circulation existed during the Cenomanian before OAE2 and that dysoxia/anoxia was caused by paleogeography rather than by ocean stagnation. The existence of restricted basins, disconnected from the deep global circulation and supplied with oxygen‐depleted waters from Oxygen Minimum Zones of the surrounding basins, played a key role in the development of dysoxic/anoxic regions. A comparison with redox‐proxy data suggests that a deep connection existed between the Pacific and Central Atlantic prior to OAE2. A shallowing of the CAS may have contributed to the establishment of enhanced anoxia in the Central Atlantic, but cannot be the only OAE2 triggering factor. The paleogeographic configuration and that of gateways appear as major factors controlling the oceanic circulation and oxygen distribution, leading to extended low‐oxygenated oceanic areas as prerequisite conditions necessary for the OAE2 to occur.
Regional Impact of Ozone Precursor Emissions on NOX and O3 Levels at ZOTTO Tall Tower in Central Siberia
Authors: Moiseenko K. B. , Vasileva A. V. , Skorokhod A. I. , Belikov I. B. , Repin A. Yu. , Shtabkin Yu. A.
Published: June 2021

Seasonal variations of the near‐surface NOX (= NO + NO2) and ozone (O3) mixing ratios at Zotino Tall Tower (ZOTTO), a remote site in central Siberia, are described for years 2007–2014. Conditional probability function analysis and back trajectories are used to determine the origins of clean (continental baseline, CB) and regional emissions‐influenced air. High NOX levels at the site are observed for air from industrial regions of western Siberia and Ural Mountains, whereas CB air originates from remote areas of North Eurasia within 55°–70°N. The estimated annual means of daytime O3 and NOX mixing ratios for CB air are 27.0 and 0.44 ppbv, correspondingly, versus the similar quantities of 27.9 and 0.79 ppbv for all data. Monthly ozone for CB air shows a distinct maximum in April, as is the case for Northern Hemisphere midlatitude baseline (NHMLB) air at the European inflow boundary according to the surface ozone data for Mace Head and Norwegian monitoring sites, and a minimum in late summer–early autumn reflecting a weak continental‐scale ozone production from biogenic sources of ozone precursors and wildfire emissions throughout the warm season. During spring and early summer under hot weather conditions, regional anthropogenic and wildfire emissions are an important source for ozone in the continental boundary layer over southern and central Siberia, resulting in surface ozone levels compared to or larger than those observed in NHMLB air. Throughout the remaining part of year, the central North Eurasia represents a sink for tropospheric ozone on a hemispheric scale.
Acceleration of Oxygen Ions in Dipolarization Events: 1. CPS Distributions
Authors: Birn J. , Hesse M. , Bingham S. T. , Turner D. L. , Nakamura R.
Published: June 2021

Using an MHD simulation of near tail reconnection associated with a flow burst and the collapse (dipolarization) of the inner tail in combination with test particle tracing we study the acceleration and flux increases of energetic oxygen ions (O+). The characteristic orbits, distributions, and acceleration mechanisms are governed by the dimensionless parameter σ = ωcitn, where ωci is the ion gyro frequency and tn a characteristic Alfvén time of the MHD simulation. For σ < 1, central plasma sheet (CPS) populations after the passage of the dipolarization front are found to resemble half‐shells in velocity space oriented toward dusk. They originate from within the CPS and are energized typically by a single encounter of the region of enhanced cross‐tail electric field associated with the flow burst. For larger σ values (σ > 1) the O+ distributions resemble more closely those of protons, consisting of two counter‐streaming field‐aligned beams and an, albeit more tenuous and irregular, ring population perpendicular to the magnetic field. The existence of the beams, however, depends on suitable earthward moving source populations in the plasma sheet boundary layer or the adjacent lobes. The acceleration to higher energies is found to indicate a charge dependence, consistent with a dominance of more highly charged ions at energies of a few hundred keV. As in earlier simulations, the simulated fluxes show large anisotropies and nongyrotropic effects, phase bunching, and spatially and temporally localized beams.
A Deep Learning Model for Forecasting Sea Surface Height Anomalies and Temperatures in the South China Sea
Authors: Shao Qi , Li Wei , Han Guijun , Hou Guangchao , Liu Siyuan , Gong Yantian , Qu Ping
Published: June 2021

The field of forecasting oceanic variables has traditionally relied on numerical models, which effectively consider the ocean's dynamic evolution and are of physical importance. However, to make the models more realistic, complicated processes need to be considered, which is difficult because their calculations are complex. In fact, information on the internal dynamic mechanisms and external driving forces of the ocean are already embedded in the time series of observations. Therefore, we can determine the patterns of ocean variations through data mining of these series to achieve forecasting. Furthermore, to predict variations in ocean processes more realistically, interactions between variables and spatial correlations should be effectively considered. Thus, inspired by available remote sensing data and advancements in deep learning technologies, we develop a hybrid model based on a statistical method and a deep learning model to predict multiple sea surface variables. A case study in the South China Sea shows that this model is highly promising for short‐term daily forecasts of the sea surface height anomaly (SSHA) and sea surface temperature (SST). When the forecast time is 10 days, the root mean square errors of this model forecasts for SSHA and SST are approximately 0.0276 m and 0.46°C, respectively, which are much smaller than those of persistence, climatology and linear regression predictions. The anomaly correlation coefficients for SSHA and SST are approximately 0.864 and 0.633, respectively. The model performs satisfactorily under both normal and typhoon weather conditions.
SOX9 is a critical regulator of TSPAN8-mediated metastasis in pancreatic cancer
Authors: Li Junjian , Chen Xiaoliang , Zhu Liqun , Lao Zhenghong , Zhou Tianhao , Zang Lijuan , Ge Weiyu , Jiang Mengyi , Xu Jingxuan , Cao Yuan , Du Shaoqian , Yu Yue , Fan Guangjian , Wang Hongxia
Published: June 2021

Pancreatic ductal adenocarcinoma (PDAC) is the deadliest cancer mainly owing to its proclivity to early metastasis and the lack of effective targeted therapeutic drugs. Hence, understanding the molecular mechanisms underlying early invasion and metastasis by PDAC is imperative for improving patient outcomes. The present study identified that upregulation of TSPAN8 expression in PDAC facilitates metastasis in vivo and in vitro. We found SOX9 as a key transcriptional regulator of TSPAN8 expression in response to EGF stimulation. SOX9 modulation was sufficient to positively regulate endogenous expression of TSPAN8, with concomitant in vitro phenotypic changes such as loss of cell–matrix adherence and increased invasion. Moreover, increased SOX9 and TSPAN8 levels were shown to correlate in human pancreatic cancer specimens and downregulated in vitro by EGFR tyrosine kinase inhibitors. High expression of SOX9 and TSPAN8 has been associated with tumor stage, poor prognosis and poor patient survival in PDAC. In conclusion, this study highlights the importance of the EGF-SOX9-TSPAN8 signaling cascade in the control of PDAC invasion and implies that TSPAN8 may be a promising novel therapeutic target for the treatment of PDAC.
A novel homeostatic loop of sorcin drives paclitaxel-resistance and malignant progression via Smad4/ZEB1/miR-142-5p in human ovarian cancer
Authors: Zhang Jinguo , Guan Wencai , Xu Xiaolin , Wang Fanchen , Li Xin , Xu Guoxiong
Published: June 2021

The primary chemotherapy of ovarian cancer (OC) often acquires chemoresistance. Sorcin (SRI), a soluble resistance-related calcium-binding protein, has been reported to be an oncogenic protein in cancer. However, the molecular mechanisms of SRI regulation and the role and aberrant expression of SRI in chemoresistant OC remain unclear. Here, we identified SRI as a key driver of paclitaxel (PTX)-resistance and explored its regulatory mechanism. Using transcriptome profiles, qRT-PCR, proteomics, Western blot, immunohistochemistry, and bioinformatics analyses, we found that SRI was overexpressed in PTX-resistant OC cells and the overexpression of SRI was related to the poor prognosis of patients. SRI was a key molecule required for growth, migration, and PTX-resistance in vitro and in vivo and was involved in epithelial–mesenchymal transition (EMT) and stemness. Mechanistic studies showed that miR-142-5p directly bound to the 3ʹ-UTR of SRI to suppress its expression, whereas a transcription factor zinc-finger E-box binding homeobox 1 (ZEB1) inhibited the transcription of miR-142-5p by directly binding to the E-box fragment in the miR-142 promoter region. Furthermore, ZEB1 was negatively regulated by SRI which physically interacted with Smad4 to block its translocation from the cytosol to the nucleus. Taken together, our findings unveil a novel homeostatic loop of SRI that drives the PTX-resistance and malignant progression via Smad4/ZEB1/miR-142-5p in human OC. Targeting this SRI/Smad4/ZEB1/miR-142-5p loop may reverse the PTX-resistance.
Interaction between HLA-G and NK cell receptor KIR2DL4 orchestrates HER2-positive breast cancer resistance to trastuzumab
Authors: Zheng Guoxu , Guo Zhangyan , Li Weimiao , Xi Wenjin , Zuo Baile , Zhang Rui , Wen Weihong , Yang An-Gang , Jia Lintao
Published: June 2021

Despite the successful use of the humanized monoclonal antibody trastuzumab (Herceptin) in the clinical treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer, the frequently occurring drug resistance remains to be overcome. The regulatory mechanisms of trastuzumab-elicited immune response in the tumor microenvironment remain largely uncharacterized. Here, we found that the nonclassical histocompatibility antigen HLA-G desensitizes breast cancer cells to trastuzumab by binding to the natural killer (NK) cell receptor KIR2DL4. Unless engaged by HLA-G, KIR2DL4 promotes antibody-dependent cell-mediated cytotoxicity and forms a regulatory circuit with the interferon-γ (IFN-γ) production pathway, in which IFN-γ upregulates KIR2DL4 via JAK2/STAT1 signaling, and then KIR2DL4 synergizes with the Fcγ receptor to increase IFN-γ secretion by NK cells. Trastuzumab treatment of neoplastic and NK cells leads to aberrant cytokine production characterized by excessive tumor growth factor-β (TGF-β) and IFN-γ, which subsequently reinforce HLA-G/KIR2DL4 signaling. In addition, TGF-β and IFN-γ impair the cytotoxicity of NK cells by upregulating PD-L1 on tumor cells and PD-1 on NK cells. Blockade of HLA-G/KIR2DL4 signaling improved the vulnerability of HER2-positive breast cancer to trastuzumab treatment in vivo. These findings provide novel insights into the mechanisms underlying trastuzumab resistance and demonstrate the applicability of combined HLA-G and PD-L1/PD-1 targeting in the treatment of trastuzumab-resistant breast cancer.
TXNIP, a novel key factor to cause Schwann cell dysfunction in diabetic peripheral neuropathy, under the regulation of PI3K/Akt pathway inhibition-induced DNMT1 and DNMT3a overexpression
Authors: Zhang Xiang , Zhao Song , Yuan Qingqing , Zhu Lin , Li Fan , Wang Hui , Kong Dezhi , Hao Jun
Published: June 2021

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus (DM) and the dysfunction of Schwann cells plays an important role in the pathogenesis of DPN. Thioredoxin-interacting protein (TXNIP) is known as an inhibitor of thioredoxin and associated with oxidative stress and inflammation. However, whether TXNIP is involved in dysfunction of Schwann cells of DPN and the exact mechanism is still not known. In this study, we first reported that TXNIP expression was significantly increased in the sciatic nerves of diabetic mice, accompanied by abnormal electrophysiological indexes and myelin sheath structure. Similarly, in vitro cultured Schwann cells TXNIP was evidently enhanced by high glucose stimulation. Again, the function experiment found that knockdown of TXNIP in high glucose-treated RSC96 cells led to a 4.12 times increase of LC3-II/LC3-I ratio and a 25.94% decrease of cleaved caspase 3/total caspase 3 ratio. Then, DNA methyltransferase (DNMT) inhibitor 5-Aza has been reported to benefit Schwann cell in DPN, and here 5-Aza treatment reduced TXNIP protein expression, improved autophagy and inhibited apoptosis in high glucose-treated RSC96 cells and the sciatic nerves of diabetic mice. Furthermore, DNMT1 and DNMT3a upregulation were found to be involved in TXNIP overexpression in high glucose-stimulated RSC96 cells. Silencing of DNMT1 and DNMT3a effectively reversed high glucose-enhanced TXNIP. Moreover, high glucose-inhibited PI3K/Akt pathway led to DNMT1, DNMT3a, and TXNIP upregulation in RSC96 cells. Knockdown of DNMT1 and DNMT3a prevented PI3K/Akt pathway inhibition-caused TXNIP upregulation in RSC96 cells. Finally, in vivo knockout of TXNIP improved nerve conduction function, increased autophagosome and LC3 expression, and decreased cleaved Caspase 3 and Bax expression in diabetic mice. Taken together, PI3K/Akt pathway inhibition mediated high glucose-induced DNMT1 and DNMT3a overexpression, leading to cell autophagy inhibition and apoptosis via TXNIP protein upregulation in Schwann cells of DPN.
Antipathogenic properties and applications of low-dimensional materials
Authors: Shaw Z. L. , Kuriakose Sruthi , Cheeseman Samuel , Dickey Michael D. , Genzer Jan , Christofferson Andrew J. , Crawford Russell J. , McConville Chris F. , Chapman James , Truong Vi Khanh , Elbourne Aaron , Walia Sumeet
Published: June 2021

A major health concern of the 21st century is the rise of multi-drug resistant pathogenic microbial species. Recent technological advancements have led to considerable opportunities for low-dimensional materials (LDMs) as potential next-generation antimicrobials. LDMs have demonstrated antimicrobial behaviour towards a variety of pathogenic bacterial and fungal cells, due to their unique physicochemical properties. This review provides a critical assessment of current LDMs that have exhibited antimicrobial behaviour and their mechanism of action. Future design considerations and constraints in deploying LDMs for antimicrobial applications are discussed. It is envisioned that this review will guide future design parameters for LDM-based antimicrobial applications.
CD45 pre-exclusion from the tips of T cell microvilli prior to antigen recognition
Authors: Jung Yunmin , Wen Lai , Altman Amnon , Ley Klaus
Published: June 2021

The tyrosine phosphatase CD45 is a major gatekeeper for restraining T cell activation. Its exclusion from the immunological synapse (IS) is crucial for T cell receptor (TCR) signal transduction. Here, we use expansion super-resolution microscopy to reveal that CD45 is mostly pre-excluded from the tips of microvilli (MV) on primary T cells prior to antigen encounter. This pre-exclusion is diminished by depleting cholesterol or by engineering the transmembrane domain of CD45 to increase its membrane integration length, but is independent of the CD45 extracellular domain. We further show that brief MV-mediated contacts can induce Ca2+ influx in mouse antigen-specific T cells engaged by antigen-pulsed antigen presenting cells (APC). We propose that the scarcity of CD45 phosphatase activity at the tips of MV enables or facilitates TCR triggering from brief T cell-APC contacts before formation of a stable IS, and that these MV-mediated contacts represent the earliest step in the initiation of a T cell adaptive immune response.
The adaptive landscape of a metallo-enzyme is shaped by environment-dependent epistasis
Authors: Anderson Dave W. , Baier Florian , Yang Gloria , Tokuriki Nobuhiko
Published: June 2021

Enzymes can evolve new catalytic activity when environmental changes present them with novel substrates. Despite this seemingly straightforward relationship, factors other than the direct catalytic target can also impact adaptation. Here, we characterize the catalytic activity of a recently evolved bacterial methyl-parathion hydrolase for all possible combinations of the five functionally relevant mutations under eight different laboratory conditions (in which an alternative divalent metal is supplemented). The resultant adaptive landscapes across this historical evolutionary transition vary in terms of both the number of “fitness peaks” as well as the genotype(s) at which they are found as a result of genotype-by-environment interactions and environment-dependent epistasis. This suggests that adaptive landscapes may be fluid and molecular adaptation is highly contingent not only on obvious factors (such as catalytic targets), but also on less obvious secondary environmental factors that can direct it towards distinct outcomes.
Environmental enrichment preserves a young DNA methylation landscape in the aged mouse hippocampus
Authors: Zocher Sara , Overall Rupert W. , Lesche Mathias , Dahl Andreas , Kempermann Gerd
Published: June 2021

The decline of brain function during aging is associated with epigenetic changes, including DNA methylation. Lifestyle interventions can improve brain function during aging, but their influence on age-related epigenetic changes is unknown. Using genome-wide DNA methylation sequencing, we here show that experiencing a stimulus-rich environment counteracts age-related DNA methylation changes in the hippocampal dentate gyrus of mice. Specifically, environmental enrichment prevented the aging-induced CpG hypomethylation at target sites of the methyl-CpG-binding protein Mecp2, which is critical to neuronal function. The genes at which environmental enrichment counteracted aging effects have described roles in neuronal plasticity, neuronal cell communication and adult hippocampal neurogenesis and are dysregulated with age-related cognitive decline in the human brain. Our results highlight the stimulating effects of environmental enrichment on hippocampal plasticity at the level of DNA methylation and give molecular insights into the specific aspects of brain aging that can be counteracted by lifestyle interventions.
Co-evolution of matrisome and adaptive adhesion dynamics drives ovarian cancer chemoresistance
Authors: Pietilä Elina A. , Gonzalez-Molina Jordi , Moyano-Galceran Lidia , Jamalzadeh Sanaz , Zhang Kaiyang , Lehtinen Laura , Turunen S. Pauliina , Martins Tomás A. , Gultekin Okan , Lamminen Tarja , Kaipio Katja , Joneborg Ulrika , Hynninen Johanna , Hietanen Sakari , Grénman Seija , Lehtonen Rainer , Hautaniemi Sampsa , Carpén Olli , Carlson Joseph W. , Lehti Kaisa
Published: June 2021

Due to its dynamic nature, the evolution of cancer cell-extracellular matrix (ECM) crosstalk, critically affecting metastasis and treatment resistance, remains elusive. Our results show that platinum-chemotherapy itself enhances resistance by progressively changing the cancer cell-intrinsic adhesion signaling and cell-surrounding ECM. Examining ovarian high-grade serous carcinoma (HGSC) transcriptome and histology, we describe the fibrotic ECM heterogeneity at primary tumors and distinct metastatic sites, prior and after chemotherapy. Using cell models from systematic ECM screen to collagen-based 2D and 3D cultures, we demonstrate that both specific ECM substrates and stiffness increase resistance to platinum-mediated, apoptosis-inducing DNA damage via FAK and β1 integrin-pMLC-YAP signaling. Among such substrates around metastatic HGSCs, COL6 was upregulated by chemotherapy and enhanced the resistance of relapse, but not treatment-naïve, HGSC organoids. These results identify matrix adhesion as an adaptive response, driving HGSC aggressiveness via co-evolving ECM composition and sensing, suggesting stromal and tumor strategies for ECM pathway targeting.
Irreversible electroporation augments checkpoint immunotherapy in prostate cancer and promotes tumor antigen-specific tissue-resident memory CD8+ T cells
Authors: Burbach Brandon J. , O’Flanagan Stephen D. , Shao Qi , Young Katharine M. , Slaughter Joseph R. , Rollins Meagan R. , Street Tami Jo L. , Granger Victoria E. , Beura Lalit. K. , Azarin Samira M. , Ramadhyani Satish , Forsyth Bruce R. , Bischof John C. , Shimizu Yoji
Published: June 2021

Memory CD8+ T cells populate non-lymphoid tissues (NLTs) following pathogen infection, but little is known about the establishment of endogenous tumor-specific tissue-resident memory T cells (TRM) during cancer immunotherapy. Using a transplantable mouse model of prostate carcinoma, here we report that tumor challenge leads to expansion of naïve neoantigen-specific CD8+ T cells and formation of a small population of non-recirculating TRM in several NLTs. Primary tumor destruction by irreversible electroporation (IRE), followed by anti-CTLA-4 immune checkpoint inhibitor (ICI), promotes robust expansion of tumor-specific CD8+ T cells in blood, tumor, and NLTs. Parabiosis studies confirm that TRM establishment following dual therapy is associated with tumor remission in a subset of cases and protection from subsequent tumor challenge. Addition of anti-PD-1 following dual IRE + anti-CTLA-4 treatment blocks tumor growth in non-responsive cases. This work indicates that focal tumor destruction using IRE combined with ICI is a potent in situ tumor vaccination strategy that generates protective tumor-specific TRM.
Mining and unearthing hidden biosynthetic potential
Authors: Scherlach Kirstin , Hertweck Christian
Published: June 2021

Genetically encoded small molecules (secondary metabolites) play eminent roles in ecological interactions, as pathogenicity factors and as drug leads. Yet, these chemical mediators often evade detection, and the discovery of novel entities is hampered by low production and high rediscovery rates. These limitations may be addressed by genome mining for biosynthetic gene clusters, thereby unveiling cryptic metabolic potential. The development of sophisticated data mining methods and genetic and analytical tools has enabled the discovery of an impressive array of previously overlooked natural products. This review shows the newest developments in the field, highlighting compound discovery from unconventional sources and microbiomes.
Notch signaling and efficacy of PD-1/PD-L1 blockade in relapsed small cell lung cancer
Authors: Roper Nitin , Velez Moises J. , Chiappori Alberto , Kim Yoo Sun , Wei Jun S. , Sindiri Sivasish , Takahashi Nobuyuki , Mulford Deborah , Kumar Suresh , Ylaya Kris , Trindade Christopher , Manukyan Irena , Brown Anna-Leigh , Trepel Jane B. , Lee Jung-Min , Hewitt Stephen , Khan Javed , Thomas Anish
Published: June 2021

Immune checkpoint blockade (ICB) benefits only a small subset of patients with small cell lung cancer (SCLC), yet the mechanisms driving benefit are poorly understood. To identify predictors of clinical benefit to ICB, we performed immunogenomic profiling of tumor samples from patients with relapsed SCLC. Tumors of patients who derive clinical benefit from ICB exhibit cytotoxic T-cell infiltration, high expression of antigen processing and presentation machinery (APM) genes, and low neuroendocrine (NE) differentiation. However, elevated Notch signaling, which positively correlates with low NE differentiation, most significantly predicts clinical benefit to ICB. Activation of Notch signaling in a NE human SCLC cell line induces a low NE phenotype, marked by increased expression of APM genes, demonstrating a mechanistic link between Notch activation, low NE differentiation and increased intrinsic tumor immunity. Our findings suggest Notch signaling as a determinant of response to ICB in SCLC.
High-pressure reversibility in a plastically flexible coordination polymer crystal
Authors: Liu Xiaojiao , Michalchuk Adam A. L. , Bhattacharya Biswajit , Yasuda Nobuhiro , Emmerling Franziska , Pulham Colin R.
Published: June 2021

Single crystals which exhibit mechanical flexibility are promising materials for advanced technological applications. Before such materials can be used, a detailed understanding of the mechanisms of bending is needed. Using single crystal X-ray diffraction and microfocus Raman spectroscopy, we study in atomic detail the high-pressure response of the plastically flexible coordination polymer [Zn(μ-Cl)2(3,5-dichloropyridine)2]n (1). Contradictory to three-point bending, quasi-hydrostatic compression of (1) is completely reversible, even following compression to over 9 GPa. A structural phase transition is observed at ca. 5 GPa. DFT calculations show this transition to result from the pressure-induced softening of low-frequency vibrations. This phase transition is not observed during three-point-bending. Microfocus synchrotron X-ray diffraction revealed that bending yields significant mosaicity, as opposed to compression. Hence, our studies indicate of overall disparate mechanical responses of bulk flexibility and quasi-hydrostatic compression within the same crystal lattice. We suspect this to be a general feature of plastically bendable materials.
ATRX promotes heterochromatin formation to protect cells from G-quadruplex DNA-mediated stress
Authors: Teng Yu-Ching , Sundaresan Aishwarya , O’Hara Ryan , Gant Vincent U. , Li Minhua , Martire Sara , Warshaw Jane N. , Basu Amrita , Banaszynski Laura A.
Published: June 2021

ATRX is a tumor suppressor that has been associated with protection from DNA replication stress, purportedly through resolution of difficult-to-replicate G-quadruplex (G4) DNA structures. While several studies demonstrate that loss of ATRX sensitizes cells to chemical stabilizers of G4 structures, the molecular function of ATRX at G4 regions during replication remains unknown. Here, we demonstrate that ATRX associates with a number of the MCM replication complex subunits and that loss of ATRX leads to G4 structure accumulation at newly synthesized DNA. We show that both the helicase domain of ATRX and its H3.3 chaperone function are required to protect cells from G4-induced replicative stress. Furthermore, these activities are upstream of heterochromatin formation mediated by the histone methyltransferase, ESET, which is the critical molecular event that protects cells from G4-mediated stress. In support, tumors carrying mutations in either ATRX or ESET show increased mutation burden at G4-enriched DNA sequences. Overall, our study provides new insights into mechanisms by which ATRX promotes genome stability with important implications for understanding impacts of its loss on human disease.
Grain-boundary-rich polycrystalline monolayer WS2 film for attomolar-level Hg2+ sensors
Authors: Liu Lixuan , Ye Kun , Lin Changqing , Jia Zhiyan , Xue Tianyu , Nie Anmin , Cheng Yingchun , Xiang Jianyong , Mu Congpu , Wang Bochong , Wen Fusheng , Zhai Kun , Zhao Zhisheng , Gong Yongji , Liu Zhongyuan , Tian Yongjun
Published: June 2021

Emerging two-dimensional (2D) layered materials have been attracting great attention as sensing materials for next-generation high-performance biological and chemical sensors. The sensor performance of 2D materials is strongly dependent on the structural defects as indispensable active sites for analyte adsorption. However, controllable defect engineering in 2D materials is still challenging. In the present work, we propose exploitation of controllably grown polycrystalline films of 2D layered materials with high-density grain boundaries (GBs) for design of ultra-sensitive ion sensors, where abundant structural defects on GBs act as favorable active sites for ion adsorption. As a proof-of-concept, our fabricated surface plasmon resonance sensors with GB-rich polycrystalline monolayer WS2 films have exhibited high selectivity and superior attomolar-level sensitivity in Hg2+ detection owing to high-density GBs. This work provides a promising avenue for design of ultra-sensitive sensors based on GB-rich 2D layered materials.