bluuebunny/crossref_metadata_2025_split huggingface dataset:
The first crystal structure of a DNA-free nuclear receptor DNA binding domain sheds light on DNA-driven allostery in the glucocorticoid receptor
Authors: Frank Filipp , Okafor C. Denise , Ortlund Eric A. 
Published: September 2018

AbstractThe glucocorticoid receptor (GR) is a steroid hormone receptor of the nuclear receptor family that regulates gene expression in response to glucocorticoid hormone signaling. Interaction with specific GR DNA binding sequences causes conformational changes in the GR DNA binding domain (DBD) that result in recruitment of specific sets of co-regulators that determine transcriptional outcomes. We have solved the crystal structure of GR DBD in its DNA-free state, the first such crystal structure from any nuclear receptor. In contrast to previous NMR structures, this crystal structure reveals that free GR DBD adopts a conformation very similar to DNA-bound states. The lever arm region is the most variable element in the free GR DBD. Molecular dynamics of the free GR DBD as well as GR DBD bound to activating and repressive DNA elements confirm lever arm flexibility in all functional states. Cluster analysis of lever arm conformations during simulations shows that DNA binding and dimerization cause a reduction in the number of conformations sampled by the lever arm. These results reveal that DNA binding and dimerization drive conformational selection in the GR DBD lever arm region and show how DNA allosterically controls GR structure and dynamics.
Clerodane furanoditerpenoids as the probable cause of toxic hepatitis induced by Tinospora crispa
Authors: Cachet Xavier , Langrand Jerôme , Riffault-Valois Ludivine , Bouzidi Chouaha , Colas Cyril , Dugay Annabelle , Michel Sylvie , Boucaud-Maitre Denis 
Published: September 2018

AbstractTinospora crispa is a popular traditional herbal plant commonly used throughout the world for treatment of various diseases, in particular type 2 diabetes mellitus. We report here a new case of toxic hepatitis in a 57-year old male patient in the French West Indies following the consumption of two aqueous extracts of fresh Tinospora crispa stems. It thus differs from two previously reported cases that concerned the chronic intake of powdered dry stems delivered in solid oral dosage forms (i.e. pellets and tablets). Liquid Chromatography-Diode Array Detection-Mass Spectrometry (LC/DAD/MS) analyses were performed on an aqueous extract of the offending sample that mimics the swallowed preparation. They revealed the presence of species-specific molecular marker borapetoside C (1) and thus enabled an unambiguous phytochemical identification. The exploration of tandem MS/MS data obtained by ultra-high performance liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-HRMS) allowed the identification of 17 additional cis-clerodane-type furanoditerpenoid lactones, analogues of 1. These results support the hypothesis that the mechanisms underlying hepatotoxicity of Tinospora crispa are the same as those encountered with furanoditerpenoids-containing plants such as Teucrium chamaedrys or Dioscorea bulbifera. In the context of type 2 diabetes treatment, we recommend that Tinospora crispa intake should be more closely monitored for signs of hepatotoxicity.
Cryovolcanism on the Earth: Origin of a Spectacular Crater in the Yamal Peninsula (Russia)
Authors: Buldovicz Sergey N. , Khilimonyuk Vanda Z. , Bychkov Andrey Y. , Ospennikov Evgeny N. , Vorobyev Sergey A. , Gunar Aleksey Y. , Gorshkov Evgeny I. , Chuvilin Evgeny M. , Cherbunina Maria Y. , Kotov Pavel I. , Lubnina Natalia V. , Motenko Rimma G. , Amanzhurov Ruslan M. 
Published: September 2018

AbstractGeological activity on icy planets and planetoids includes cryovolcanism. Until recently, most research on terrestrial permafrost has been engineering-oriented, and many related phenomena have received too little attention. Although fast processes in the Earth’s cryosphere were known before, they have never been attributed to cryovolcanism. The discovery of a couple of tens of meters wide crater in the Yamal Peninsula aroused numerous hypotheses of its origin, including a meteorite impact or migration of deep gas as a result of global warming. However, the origin of the Yamal crater can be explained in terms of cryospheric processes. Thus, the Yamal crater appears to result from collapse of a large pingo, which formed within a thaw lake when it shoaled and dried out allowing a large talik (that is layer or body of unfrozen ground in a permafrost area) below it to freeze back. The pingo collapsed under cryogenic hydrostatic pressure built up in the closed system of the freezing talik. This happened before the freezing completed, when a core of wet ground remained unfrozen and stored a huge amount of carbon dioxide dissolved in pore water. This eventually reached gas-phase saturation, and the resulting overpressure came to exceed the lithospheric confining stress and the strength of the overlying ice. As the pingo exploded, the demarcation of the crater followed the cylindrical shape of the remnant talik core.
Microfabricated tuneable and transferable porous PDMS membranes for Organs-on-Chips
Authors: Quirós-Solano W. F. , Gaio N. , Stassen O. M. J. A. , Arik Y. B. , Silvestri C. , Van Engeland N. C. A. , Van der Meer A. , Passier R. , Sahlgren C. M. , Bouten C. V. C. , van den Berg A. , Dekker R. , Sarro P. M. 
Published: September 2018

AbstractWe present a novel and highly reproducible process to fabricate transferable porous PDMS membranes for PDMS-based Organs-on-Chips (OOCs) using microelectromechanical systems (MEMS) fabrication technologies. Porous PDMS membranes with pore sizes down to 2.0 μm in diameter and a wide porosity range (2–65%) can be fabricated. To overcome issues normally faced when using replica moulding and extend the applicability to most OOCs and improve their scalability and reproducibility, the process includes a sacrificial layer to easily transfer the membranes from a silicon carrier to any PDMS-based OOC. The highly reliable fabrication and transfer method does not need of manual handling to define the pore features (size, distribution), allowing very thin (<10 μm) functional membranes to be transferred at chip level with a high success rate (85%). The viability of cell culturing on the porous membranes was assessed by culturing two different cell types on transferred membranes in two different OOCs. Human umbilical endothelial cells (HUVEC) and MDA-MB-231 (MDA) cells were successfully cultured confirming the viability of cell culturing and the biocompatibility of the membranes. The results demonstrate the potential of controlling the porous membrane features to study cell mechanisms such as transmigrations, monolayer formation, and barrier function. The high control over the membrane characteristics might consequently allow to intentionally trigger or prevent certain cellular responses or mechanisms when studying human physiology and pathology using OOCs.
Pharmacological difference between degrader and inhibitor against oncogenic BCR-ABL kinase
Authors: Shibata Norihito , Shimokawa Kenichiro , Nagai Katsunori , Ohoka Nobumichi , Hattori Takayuki , Miyamoto Naoki , Ujikawa Osamu , Sameshima Tomoya , Nara Hiroshi , Cho Nobuo , Naito Mikihiko 
Published: September 2018

AbstractChronic myelogenous leukemia (CML) is characterized by the oncogenic fusion protein, BCR-ABL protein kinase, against which clinically useful inhibitors have been developed. An alternative approach to treat CML is to degrade the BCR-ABL protein. Recently, potent degraders against BCR-ABL have been developed by conjugating dasatinib to ligands for E3 ubiquitin ligases. Since the degraders contain the dasatinib moiety, they also inhibit BCR-ABL kinase activity, which complicates our understanding of the impact of BCR-ABL degradation by degraders in CML growth inhibition. To address this issue, we chose DAS-IAP, as a potent BCR-ABL degrader, and developed a structurally related inactive degrader, DAS-meIAP, which inhibits kinase activity but does not degrade the BCR-ABL protein. DAS-IAP showed slightly weaker activity than DAS-meIAP in inhibiting cell growth when CML cells were treated for 48 h. However, DAS-IAP showed sustained growth inhibition even when the drug was removed after short-term treatment, whereas CML cell growth rapidly resumed following removal of DAS-meIAP and dasatinib. Consistently, suppression of BCR-ABL levels and downstream kinase signaling were maintained after DAS-IAP removal, whereas kinase signaling rapidly recovered following removal of DAS-meIAP and dasatinib. These results indicate that BCR-ABL degrader shows more sustained inhibition of CML cell growth than ABL kinase inhibitor.
Effective passivation of Ag nanowire network by transparent tetrahedral amorphous carbon film for flexible and transparent thin film heaters
Authors: Seok Hae-Jun , Kim Jong-Kuk , Kim Han-Ki 
Published: September 2018

AbstractWe developed effective passivation method of flexible Ag nanowire (NW) network electrodes using transparent tetrahedral amorphous carbon (ta-C) film prepared by filtered cathode vacuum arc (FCVA) coating. Even at room temperature process of FCVA, the ta-C passivation layer effectively protect Ag NW network electrode and improved the ambient stability of Ag NW network without change of sheet resistance of Ag NW network. In addition, ta-C coated Ag NW electrode showed identical critical inner and outer bending radius to bare Ag NW due to the thin thickness of ta-C passivation layer. The time-temperature profiles demonstrate that the performance of the transparent and flexible thin film heater (TFH) with the ta-C/Ag NW network is better than that of a TFH with Ag NW electrodes due to thermal stability of FCVA grown ta-C layer. In addition, the transparent and flexible TFHs with ta-C/Ag NW showed robustness against external force due to its high hardness and wear resistance. This indicates that the FCVA coated ta-C is promising passivation and protective layer for chemically weak Ag NW network electrodes against sulfur in ambient.
Sub-wavelength terahertz imaging through optical rectification
Authors: Sanjuan Federico , Gaborit Gwenaël , Coutaz Jean-Louis 
Published: September 2018

AbstractWe record a sub-wavelength terahertz image of a caster sugar grain thanks to optical rectification in the sample excited with a femtosecond laser beam. The lateral spatial resolution of this technique is given by the laser spot size at the sample and here its measured value is 50 μm, i.e. ~λ/12. We give an estimation of the ultimate resolution that could be achieved with this method.
Advanced fabrication of biosensor on detection of Glypican-1 using S-Acetylmercaptosuccinic anhydride (SAMSA) modification of antibody
Authors: Dai Yifan , Abbasi Kevin , DePietro Michael , Butler Samantha , Liu Chung Chiun 
Published: September 2018

AbstractGlypican-1 (GPC-1) has been recognized as biomarker of pancreatic cancer. Quantification of GPC-1 level is also pivotal to breast cancer and prostate cancer’s patients. We hereby report the first biosensor for GPC-1 detection. Instead of using crosslinking technique and surface immobilization of antibody, we applied a novel method for biosensor fabrication, using S-Acetylmercaptosuccinic anhydride (SAMSA) to modify the Anti-GPC-1 producing a thiol-linked Anti-GPC-1. The thiol-linked Anti-GPC-1 was then directly formed a single-layer antibody layer on the gold biosensor, minimizing the biosensor preparation steps significantly. Time of Flight Secondary Ions Mass Spectroscopy (TOF-SIMS) characterization verified the thiol-linked antibody layer and demonstrated a unique perspective for surface protein characterization. Differential pulse voltammetry (DPV) was applied to quantify GPC-1 antigen in undiluted human serum with a concentration range of 5,000 pg/µL to 100 pg/µL. The performance of this newly designed biosensor was also compared with modified self-assembled monolayer system fabricated biosensor, demonstrating the high-sensitivity and high-reproducibility of the SAMSA modified antibody based biosensor. This simple fabrication method can also expand to detection of other biomolecules. The simplified operation process shows great potential in clinical application development.
Interaction of TBC1D9B with Mammalian ATG8 Homologues Regulates Autophagic Flux
Authors: Liao Yong , Li Min , Chen Xiaoyun , Jiang Yu , Yin Xiao-Ming 
Published: September 2018

AbstractAutophagosomes are double-membraned vesicles with cytosolic components. Their destination is to fuse with the lysosome to degrade the enclosed cargo. However, autophagosomes may be fused with other membrane compartments and possibly misguided by the RAB molecules from these compartments. The mechanisms ensuring the proper trafficking are not well understood. Yeast ATG8 and its mammalian homologues are critically involved in the autophagosome formation and expansion. We hypothesized that they could be also involved in the regulation of autophagosome trafficking. Using the yeast two-hybrid system, we found that TBC1D9B, a GTPase activating protein for RAB11A, interacted with LC3B. TBC1D9B could also interact with other mammalian ATG8 homologues. This interaction was confirmed with purified proteins in vitro, and by co-immunoprecipitation in vivo. The interacting domain of TBC1D9B with LC3 was further determined, which is unique and different from the known LC3-interacting region previously defined in other LC3-interacting molecules. Functionally, TBC1D9B could be co-localized with LC3B on the autophagosome membranes. Inhibition of TBC1D9B suppressed the turnover of membrane-bound LC3B and the autophagic degradation of long-lived proteins. TBC1D9B can thus positively regulate autophagic flux, possibly through its GTPase activity to inactivate RAB11A, facilitating the proper destination of the autophagosomes to the degradation.
Hypercapnia Alters Expression of Immune Response, Nucleosome Assembly and Lipid Metabolism Genes in Differentiated Human Bronchial Epithelial Cells
Authors: Casalino-Matsuda S. Marina , Wang Naizhen , Ruhoff Peder T. , Matsuda Hiroaki , Nlend Marie C. , Nair Aisha , Szleifer Igal , Beitel Greg J. , Sznajder Jacob I. , Sporn Peter H. S. 
Published: September 2018

AbstractHypercapnia, the elevation of CO2in blood and tissues, commonly occurs in severe acute and chronic respiratory diseases, and is associated with increased risk of mortality. Recent studies have shown that hypercapnia adversely affects innate immunity, host defense, lung edema clearance and cell proliferation. Airway epithelial dysfunction is a feature of advanced lung disease, but the effect of hypercapnia on airway epithelium is unknown. Thus, in the current study we examined the effect of normoxic hypercapnia (20% CO2for 24 h) vs normocapnia (5% CO2), on global gene expression in differentiated normal human airway epithelial cells. Gene expression was assessed on Affymetrix microarrays, and subjected to gene ontology analysis for biological process and cluster-network representation. We found that hypercapnia downregulated the expression of 183 genes and upregulated 126. Among these, major gene clusters linked to immune responses and nucleosome assembly were largely downregulated, while lipid metabolism genes were largely upregulated. The overwhelming majority of these genes were not previously known to be regulated by CO2. These changes in gene expression indicate the potential for hypercapnia to impact bronchial epithelial cell function in ways that may contribute to poor clinical outcomes in patients with severe acute or advanced chronic lung diseases.
HISDAC-US, historical settlement data compilation for the conterminous United States over 200 years
Authors: Leyk Stefan , Uhl Johannes H. 
Published: September 2018

AbstractHuman settlement plays a key role in understanding social processes such as urbanization and interactions between human and environmental systems but not much is known about the landscape evolution before the era of operational remote sensing technology. In this study, housing and property databases are used to create new gridded settlement layers describing human settlement processes at fine spatial and temporal resolution in the conterminous United States between 1810 and 2015. The main products are a raster composite layer representing the year of first settlement, and a raster time series of built-up intensity representing the sum of building areas in a pixel. Several accompanying uncertainty surfaces are provided to ensure the user is informed about inherent spatial, temporal and thematic uncertainty in the data. A validation study using high quality reference data confirms high levels of accuracy of the resulting data products. These settlement data will be of great interest in disciplines in which the long-term evolution of human settlement represents crucial information to explore novel research questions.
The XXL Survey
Authors: Ricci M. , Benoist C. , Maurogordato S. , Adami C. , Chiappetti L. , Gastaldello F. , Guglielmo V. , Poggianti B. , Sereno M. , Adam R. , Arnouts S. , Cappi A. , Koulouridis E. , Pacaud F. , Pierre M. , Ramos-Ceja M. E. 
Published: September 2018

Context. The luminosity function (LF) is a powerful statistical tool used to describe galaxies and learn about their evolution. In particular, the LFs of galaxies inside clusters allow us to better understand how galaxies evolve in these dense environments. Knowledge of the LFs of galaxies in clusters is also crucial for clusters studies in the optical and near-infrared (NIR) as they encode, along with their density profiles, most of their observational properties. However, no consensus has been reached yet about the evolution of the cluster galaxy LF with halo mass and redshift.
Aims. The main goal of this study is to investigate the LF of a sample of 142 X-ray selected clusters, with spectroscopic redshift confirmation and a well defined selection function, spanning a wide redshift and mass range, and to test the LF dependence on cluster global properties, in a homogeneous and unbiased way.
Methods. Our study is based on the Canada–France–Hawaii Telescope Legacy Survey (CFHTLS) photometric galaxy catalogue, associated with photometric redshifts. We constructed LFs inside a scaled radius using a selection in photometric redshift around the cluster spectroscopic redshift in order to reduce projection effects. The width of the photometric redshift selection was carefully determined to avoid biasing the LF and depended on both the cluster redshift and the galaxy magnitudes. The purity was then enhanced by applying a precise background subtraction. We constructed composite luminosity functions (CLFs) by stacking the individual LFs and studied their evolution with redshift and richness, analysing separately the brightest cluster galaxy (BCG) and non-BCG members. We fitted the dependences of the CLFs and BCG distributions parameters with redshift and richness conjointly in order to distinguish between these two effects.
Results. We find that the usual photometric redshift selection methods can bias the LF estimate if the redshift and magnitude dependence of the photometric redshift quality is not taken into account. Our main findings concerning the evolution of the galaxy luminosity distribution with redshift and richness are that, in the inner region of clusters and in the redshift-mass range we probe (about 0 < z < 1 and 1013 M⊙ < M500 < 5 × 1014 M⊙), the bright part of the LF (BCG excluded) does not depend much on mass or redshift except for its amplitude, whereas the BCG luminosity increases both with redshift and richness.
Spectral gradient of the thermal millimetre continuum as a diagnostic for optical thickness in the solar atmosphere
Authors: Rodger A. S. , Labrosse N. 
Published: September 2018

Aims. In this Letter we aim to show how the gradient of the thermal millimetre continuum spectrum, as emitted from the quiet solar atmosphere, may be used as a diagnostic for the optical thickness regime at the centre of the observing frequency band.
Methods. We show the theoretical derivation of the gradient of the millimetre continuum for both logarithmic- and linear-scale spectra. We compare this expression with the empirical relationship between the slope of the millimetre continuum spectrum and the plasma optical thickness computed from both isothermal and multi-thermal two-dimensional cylindrical radiative transfer models.
Results. It is found that the logarithmic-scale spectral gradient provides a clear diagnostic for the optical thickness regime for both isothermal and multi-thermal plasmas, provided that a suitable correction is made for a non-constant gaunt factor over the frequency band. For the use of observers we present values for this correction at all ALMA bands and at a wide range of electron temperatures.
Conclusions. We find that the spectral gradient can be used to find (a) whether the source is fully optically thin, (b) the optical thickness of the source if it lies within the transitional regime between optically thin and thick plasma (τ ≈ 10−1−101), or (c) whether the source is fully optically thick for an isothermal plasma. A multi-thermal plasma will act the same as an isothermal plasma for case (a), however, the transitional regime will only extend from τ ≈ 10−1 to τ ≈ 100. Above τ = 1 the slope of the continuum will depend increasingly on the temperature gradient, as well as the optical thickness, reducing the reliability of the diagnostic.
Occurrence and genotyping of Giardia duodenalis and Cryptosporidium in pre-weaned dairy calves in central Sichuan province, China
Authors: Zhong Zhijun , Dan Jiaming , Yan Guangwen , Tu Rui , Tian Yinan , Cao Suizhong , Shen Liuhong , Deng Junliang , Yu Shumin , Geng Yi , Gu Xiaobin , Wang Ya , Liu Haifeng , Peng Guangneng 
Published: September 2018

Giardia duodenalis and Cryptosporidium spp. are common human and animal pathogens. They have increasingly been reported in dairy calves in recent years; however, multilocus genotyping information for G. duodenalis and Cryptosporidium infecting pre-weaned dairy calves in southwestern China is limited. In the present study, the prevalence of G. duodenalis and Cryptosporidium spp. in pre-weaned dairy calves in central Sichuan province was determined and the pathogens were analyzed molecularly. Of 278 fecal samples from pre-weaned dairy calves, 26 (9.4%) were positive for G. duodenalis and 40 (14.4%) were positive for Cryptosporidium spp. Cryptosporidium bovis (n = 28), Cryptosporidium ryanae (n = 5) and Cryptosporidium parvum (n = 7) were detected. All seven C. parvum isolates were successfully subtyped based on the gp60 gene sequence, and only IIdA15G1 was detected. Multilocus sequence typing of G. duodenalis based on beta-giardin (bg), triose phosphate isomerase (tpi) and glutamate dehydrogenase (gdh) genes revealed 19 different assemblage E multilocus genotypes (two known and 17 unpublished genotypes). Based on eBURST analysis, a high degree of genetic diversity within assemblage E was observed in pre-weaned dairy calves in Sichuan province. To the best of our knowledge, this is the first study using multilocus sequence typing and eBURST analysis to characterize G. duodenalis in pre-weaned dairy calves in southwestern China.