bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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

AbstractThe 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

AbstractSeasonal 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

AbstractUsing 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

AbstractThe 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

AbstractPancreatic 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

AbstractThe 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

AbstractDespite 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

AbstractDiabetic 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

AbstractA 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

AbstractThe 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

AbstractEnzymes 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

AbstractThe 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

AbstractDue 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.