bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upper Plate Controls on the Formation of Broken Foreland Basins in the Andean Retroarc Between 26°S and 28°S: From Cretaceous Rifting to Paleogene and Miocene Broken Foreland Basins
Authors: Zapata S. , Sobel E. R. , Del Papa C. , Glodny J. 
Published: June 2020

AbstractMarked along‐strike changes in stratigraphy, mountain belt morphology, basement exhumation, and deformation styles characterize the Andean retroarc; these changes have previously been related to spatiotemporal variations in the subduction angle. We modeled new apatite fission track and apatite (U‐Th‐Sm)/He data from nine ranges located between 26°S and 28°S. Using new and previously published data, we constructed a Cretaceous to Pliocene paleogeographic model that delineates a four‐stage tectonic evolution: extensional tectonics during the Cretaceous (120–75 Ma), the formation of a broken foreland basin between 55 and 30 Ma, reheating due to burial beneath sedimentary rocks (18–13 Ma), and deformation, exhumation, and surface uplift during the Late Miocene and the Pliocene (13–3 Ma). Our model highlights how preexisting upper plate structures control the deformation patterns of broken foreland basins. Because retroarc deformation predates flat‐slab subduction, we propose that slab anchoring may have been the precursor of Eocene–Oligocene compression in the Andean retroarc. Our model challenges models which consider broken foreland basins and retroarc deformation in the NW Argentinian Andes to be directly related to Miocene flat subduction.
An Evaluation of the Large‐Scale Atmospheric Circulation and Its Variability in CESM2 and Other CMIP Models
Authors: Simpson Isla R. , Bacmeister Julio , Neale Richard B. , Hannay Cecile , Gettelman Andrew , Garcia Rolando R. , Lauritzen Peter H. , Marsh Daniel R. , Mills Michael J. , Medeiros Brian , Richter Jadwiga H. 
Published: June 2020

AbstractThe Community Earth System Model 2 (CESM2) is the latest Earth System Model developed by the National Center for Atmospheric Research in collaboration with the university community and is significantly advanced in most components compared to its predecessor (CESM1). Here, CESM2's representation of the large‐scale atmospheric circulation and its variability is assessed. Further context is providedthrough comparison to the CESM1 large ensemble and other models from the Coupled Model Intercomparison Project (CMIP5 and CMIP6). This includes an assessment of the representation of jet streams and storm tracks, stationary waves, the global divergent circulation, the annular modes, the North Atlantic Oscillation, and blocking. Compared to CESM1, CESM2 is substantially improved in the representation of the storm tracks, Northern Hemisphere (NH) stationary waves, NH winter blocking and the global divergent circulation. It ranks within the top 10% of CMIP class models in many of these features. Some features of the Southern Hemisphere (SH) circulation have degraded, such as the SH jet strength, stationary waves, and blocking, although the SH jet stream is placed at approximately the correct location. This analysis also highlights systematic deficiencies in these features across the new CMIP6 archive, such as the continued tendency for the SH jet stream to be placed too far equatorward, the North Atlantic westerlies to be too strong over Europe, the storm tracks as measured by low‐level meridional wind variance to be too weak and a lack of blocking in the North Atlantic sector.
Common-path interferometric label-free protein sensing with resonant dielectric nanostructures
Authors: Barth Isabel , Conteduca Donato , Reardon Christopher , Johnson Steven , Krauss Thomas F. 
Published: June 2020

AbstractResearch toward photonic biosensors for point-of-care applications and personalized medicine is driven by the need for high-sensitivity, low-cost, and reliable technology. Among the most sensitive modalities, interferometry offers particularly high performance, but typically lacks the required operational simplicity and robustness. Here, we introduce a common-path interferometric sensor based on guided-mode resonances to combine high performance with inherent stability. The sensor exploits the simultaneous excitation of two orthogonally polarized modes, and detects the relative phase change caused by biomolecular binding on the sensor surface. The wide dynamic range of the sensor, which is essential for fabrication and angle tolerance, as well as versatility, is controlled by integrating multiple, tuned structures in the field of view. This approach circumvents the trade-off between sensitivity and dynamic range, typical of other phase-sensitive modalities, without increasing complexity. Our sensor enables the challenging label-free detection of procalcitonin, a small protein (13 kDa) and biomarker for infection, at the clinically relevant concentration of 1 pg mL−1, with a signal-to-noise ratio of 35. This result indicates the utility for an exemplary application in antibiotic guidance, and opens possibilities for detecting further clinically or environmentally relevant small molecules with an intrinsically simple and robust sensing modality.
Dendritic cells-derived interferon-λ1 ameliorated inflammatory bone destruction through inhibiting osteoclastogenesis
Authors: Chen Yueqi , Wang Yiran , Tang Ruohui , Yang Jing , Dou Ce , Dong Yutong , Sun Dong , Zhang Chengmin , Zhang Lincheng , Tang Yong , Dai Qijie , Luo Fei , Xu Jianzhong , Dong Shiwu 
Published: June 2020

AbstractBone infection contributing to inflammatory osteolysis is common in orthopedic surgery. The dynamic balance between bone formation and bone resorption is destroyed due to excessive osteoclast fusion and differentiation, which results in severe bone matrix loss. Many therapeutic approaches that restrain osteoclast formation and function act as efficient ways to prevent inflammatory bone erosion. We have demonstrated for the first time that dendritic cells-derived interferon-λ1 (IFN-λ1) inhibited inflammatory bone destruction in vivo and explored its underlying mechanisms on osteoclast formation in vitro. We found that IFN-λ1 was highly expressed in infectious bone tissue compared with that of non-infectious bone tissue. Additionally, dendritic cells marker genes such as CD80, CD86, and CD1a were higher expressed in infectious bone tissue than that of non-infectious bone tissue. Dendritic cells that were pretreated with LPS showed high expression of IFN-λ1. Moreover, conditioned medium of LPS-pretreated dendritic cells significantly inhibited osteoclast differentiation, as determined by TRAP staining assay. This suppressive effect was reversed by adding an IFN-λ1 monoclonal antibody. It was also investigated whether exogenous IFN-λ1 restrained osteoclastogenesis, bone resorption, F-actin ring formation, osteoclast-specific gene expression, release of pro-inflammatory cytokines, and translocation of p65 and NFATc1 by preventing the NF-κB signaling pathway and NLRP3 inflammasome formation, as well as by inducing the JAK-STAT signaling pathways in vitro. In vivo study indicated that IFN-λ1 prevents lipopolysaccharide (LPS)-induced inflammatory bone destruction by inhibiting excessive osteoclast fusion and bone resorption activity. In conclusion, our findings confirmed that dendritic cells-derived IFN-λ1 could attenuate osteoclast formation and bone resorptive activity in vitro and in vivo. These novel findings pave the way for the use of exogenous IFN-λ1 as a potential therapeutic treatment for excessive osteoclast-related diseases, such as inflammatory osteolysis, by regulating osteoclastogenesis to maintain the dynamic balance between bone formation and bone resorption.
Interleukin-6 derived from cancer-associated fibroblasts attenuates the p53 response to doxorubicin in prostate cancer cells
Authors: Cheteh Emarndeena H. , Sarne Victoria , Ceder Sophia , Bianchi Julie , Augsten Martin , Rundqvist Helene , Egevad Lars , Östman Arne , Wiman Klas G. 
Published: June 2020

AbstractCancer-associated fibroblasts (CAFs) promote tumor growth and progression, and increase drug resistance through several mechanisms. We have investigated the effect of CAFs on the p53 response to doxorubicin in prostate cancer cells. We show that CAFs produce interleukin-6 (IL-6), and that IL-6 attenuates p53 induction and upregulation of the pro-apoptotic p53 target Bax upon treatment with doxorubicin. This is associated with increased levels of MDM2 mRNA, Mdm2 protein bound to p53, and ubiquitinated p53. IL-6 also inhibited doxorubicin-induced cell death. Inhibition of JAK or STAT3 alleviated this effect, indicating that IL-6 attenuates p53 via the JAK/STAT signaling pathway. These results suggest that CAF-derived IL-6 plays an important role in protecting cancer cells from chemotherapy and that inhibition of IL-6 could have significant therapeutic value.
Molecule-based nonlinear optical switch with highly tunable on-off temperature using a dual solid solution approach
Authors: Zhang Shi-Yong , Shu Xia , Zeng Ying , Liu Qing-Yan , Du Zi-Yi , He Chun-Ting , Zhang Wei-Xiong , Chen Xiao-Ming 
Published: June 2020

AbstractNonlinear optical switches that reversibly convert between on/off states by thermal stimuli are promising for applications in the fields of photoelectronics and photonics. Currently one main drawback for practical application lies in the control of their switch temperature, especially for the temperature range near room temperature. By mixed melting treatment, here we describe an alloy-like nonlinear optical switch with tunable switch temperature via a dual solid solution approach within the coordination polymer system. We initially prepare a coordination polymer (i-PrNHMe2)[Cd(SCN)3], which functions as a high-contrast thermoresponsive nonlinear optical switch originating from a phase transition at around 328 K. Furthermore, by taking advantage of a synergistic dual solid solution effect, the melt mixing of it with its analogue (MeNHEt2)[Cd(SCN)3], which features an unequal anionic chain templated by an isomeric ammonium, can afford coordination polymer solid solutions with switch temperatures that are tunable in a range of 273–328 K merely by varying the component ratio.
Human beige adipocytes for drug discovery and cell therapy in metabolic diseases
Authors: Singh Amar M. , Zhang Liang , Avery John , Yin Amelia , Du Yuhong , Wang Hui , Li Zibo , Fu Haian , Yin Hang , Dalton Stephen 
Published: June 2020

AbstractHuman beige adipocytes (BAs) have potential utility for the development of therapeutics to treat diabetes and obesity-associated diseases. Although several reports have described the generation of beige adipocytes in vitro, their potential utility in cell therapy and drug discovery has not been reported. Here, we describe the generation of BAs from human adipose-derived stem/stromal cells (ADSCs) in serum-free medium with efficiencies >90%. Molecular profiling of beige adipocytes shows them to be similar to primary BAs isolated from human tissue. In vitro, beige adipocytes exhibit uncoupled mitochondrial respiration and cAMP-induced lipolytic activity. Following transplantation, BAs increase whole-body energy expenditure and oxygen consumption, while reducing body-weight in recipient mice. Finally, we show the therapeutic utility of BAs in a platform for high-throughput drug screening (HTS). These findings demonstrate the potential utility of BAs as a cell therapeutic and as a tool for the identification of drugs to treat metabolic diseases.
Direct transfer of tri- and di-fluoroethanol units enabled by radical activation of organosilicon reagents
Authors: Chen Xiang , Gong Xingxing , Li Zhengyu , Zhou Gang , Zhu Zhihong , Zhang Weilu , Liu Shanshan , Shen Xiao 
Published: June 2020

AbstractTrifluoroethanol and difluoroethanol units are important motifs in bioactive molecules, but the methods to direct incorporate these units are limited. Herein, we report two organosilicon reagents for the transfer of trifluoroethanol and difluoroethanol units into molecules. Through intramolecular C-Si bond activation by alkoxyl radicals, these reagents were applied in allylation, alkylation and alkenylation reactions, enabling efficient synthesis of various tri(di)fluoromethyl group substituted alcohols. The broad applicability and general utility of the approach are highlighted by late-stage introduction of these fluoroalkyl groups to complex molecules, and the synthesis of antitumor agent Z and its difluoromethyl analog Z′.
Low-dose phase retrieval of biological specimens using cryo-electron ptychography
Authors: Zhou Liqi , Song Jingdong , Kim Judy S. , Pei Xudong , Huang Chen , Boyce Mark , Mendonça Luiza , Clare Daniel , Siebert Alistair , Allen Christopher S. , Liberti Emanuela , Stuart David , Pan Xiaoqing , Nellist Peter D. , Zhang Peijun , Kirkland Angus I. , Wang Peng 
Published: June 2020

AbstractCryo-electron microscopy is an essential tool for high-resolution structural studies of biological systems. This method relies on the use of phase contrast imaging at high defocus to improve information transfer at low spatial frequencies at the expense of higher spatial frequencies. Here we demonstrate that electron ptychography can recover the phase of the specimen with continuous information transfer across a wide range of the spatial frequency spectrum, with improved transfer at lower spatial frequencies, and as such is more efficient for phase recovery than conventional phase contrast imaging. We further show that the method can be used to study frozen-hydrated specimens of rotavirus double-layered particles and HIV-1 virus-like particles under low-dose conditions (5.7 e/Å2) and heterogeneous objects in an Adenovirus-infected cell over large fields of view (1.14 × 1.14 μm), thus making it suitable for studies of many biologically important structures.
Human norovirus targets enteroendocrine epithelial cells in the small intestine
Authors: Green Kim Y. , Kaufman Stuart S. , Nagata Bianca M. , Chaimongkol Natthawan , Kim Daniel Y. , Levenson Eric A. , Tin Christine M. , Yardley Allison Behrle , Johnson Jordan A. , Barletta Ana Beatriz F. , Khan Khalid M. , Yazigi Nada A. , Subramanian Sukanya , Moturi Sangeetha R. , Fishbein Thomas M. , Moore Ian N. , Sosnovtsev Stanislav V. 
Published: June 2020

AbstractHuman noroviruses are a major cause of diarrheal illness, but pathogenesis is poorly understood. Here, we investigate the cellular tropism of norovirus in specimens from four immunocompromised patients. Abundant norovirus antigen and RNA are detected throughout the small intestinal tract in jejunal and ileal tissue from one pediatric intestinal transplant recipient with severe gastroenteritis. Negative-sense viral RNA, a marker of active viral replication, is found predominantly in intestinal epithelial cells, with chromogranin A-positive enteroendocrine cells (EECs) identified as a permissive cell type in this patient. These findings are consistent with the detection of norovirus-positive EECs in the other three immunocompromised patients. Investigation of the signaling pathways induced in EECs that mediate communication between the gut and brain may clarify mechanisms of pathogenesis and lead to the development of in vitro model systems in which to evaluate norovirus vaccines and treatment.
A nanomaterials discovery robot for the Darwinian evolution of shape programmable gold nanoparticles
Authors: Salley Daniel , Keenan Graham , Grizou Jonathan , Sharma Abhishek , Martín Sergio , Cronin Leroy 
Published: June 2020

AbstractThe fabrication of nanomaterials from the top-down gives precise structures but it is costly, whereas bottom-up assembly methods are found by trial and error. Nature evolves materials discovery by refining and transmitting the blueprints using DNA mutations autonomously. Genetically inspired optimisation has been used in a range of applications, from catalysis to light emitting materials, but these are not autonomous, and do not use physical mutations. Here we present an autonomously driven materials-evolution robotic platform that can reliably optimise the conditions to produce gold-nanoparticles over many cycles, discovering new synthetic conditions for known nanoparticle shapes using the opto-electronic properties as a driver. Not only can we reliably discover a method, encoded digitally to synthesise these materials, we can seed in materials from preceding generations to engineer more sophisticated architectures. Over three independent cycles of evolution we show our autonomous system can produce spherical nanoparticles, rods, and finally octahedral nanoparticles by using our optimized rods as seeds.
AGO-bound mature miRNAs are oligouridylated by TUTs and subsequently degraded by DIS3L2
Authors: Yang Acong , Shao Tie-Juan , Bofill-De Ros Xavier , Lian Chuanjiang , Villanueva Patricia , Dai Lisheng , Gu Shuo 
Published: June 2020

AbstractMicroRNAs (miRNAs) associated with Argonaute proteins (AGOs) regulate gene expression in mammals. miRNA 3’ ends are subject to frequent sequence modifications, which have been proposed to affect miRNA stability. However, the underlying mechanism is not well understood. Here, by genetic and biochemical studies as well as deep sequencing analyses, we find that AGO mutations disrupting miRNA 3’ binding are sufficient to trigger extensive miRNA 3’ modifications in HEK293T cells and in cancer patients. Comparing these modifications in TUT4, TUT7 and DIS3L2 knockout cells, we find that TUT7 is more robust than TUT4 in oligouridylating mature miRNAs, which in turn leads to their degradation by the DIS3L2 exonuclease. Our findings indicate a decay machinery removing AGO-associated miRNAs with an exposed 3’ end. A set of endogenous miRNAs including miR-7, miR-222 and miR-769 are targeted by this machinery presumably due to target-directed miRNA degradation.
A supramolecular system that strictly follows the binding mechanism of conformational selection
Authors: Yang Liu-Pan , Zhang Li , Quan Mao , Ward Jas S. , Ma Yan-Long , Zhou Hang , Rissanen Kari , Jiang Wei 
Published: June 2020

AbstractInduced fit and conformational selection are two dominant binding mechanisms in biology. Although induced fit has been widely accepted by supramolecular chemists, conformational selection is rarely studied with synthetic systems. In the present research, we report a macrocyclic host whose binding mechanism is unambiguously assigned to conformational selection. The kinetic and thermodynamic aspects of this system are studied in great detail. It reveals that the kinetic equation commonly used for conformational selection is strictly followed here. In addition, two mathematical models are developed to determine the association constants of the same guest to the two host conformations. A “conformational selectivity factor” is defined to quantify the fidelity of conformational selection. Many details about the kinetic and thermodynamic aspects of conformational selection are revealed by this synthetic system. The conclusion and the mathematical models reported here should be helpful in understanding complex molecular recognition in both biological and synthetic systems.
The impact of climate and antigenic evolution on seasonal influenza virus epidemics in Australia
Authors: Lam Edward K. S. , Morris Dylan H. , Hurt Aeron C. , Barr Ian G. , Russell Colin A. 
Published: June 2020

AbstractAlthough seasonal influenza viruses circulate globally, prevention and treatment occur at the level of regions, cities, and communities. At these scales, the timing, duration and magnitude of epidemics vary substantially, but the underlying causes of this variation are poorly understood. Here, based on analyses of a 15-year city-level dataset of 18,250 laboratory-confirmed and antigenically-characterised influenza virus infections from Australia, we investigate the effects of previously hypothesised environmental and virological drivers of influenza epidemics. We find that anomalous fluctuations in temperature and humidity do not predict local epidemic onset timings. We also find that virus antigenic change has no consistent effect on epidemic size. In contrast, epidemic onset time and heterosubtypic competition have substantial effects on epidemic size and composition. Our findings suggest that the relationship between influenza population immunity and epidemiology is more complex than previously supposed and that the strong influence of short-term processes may hinder long-term epidemiological forecasts.
Quantifying CDK inhibitor selectivity in live cells
Authors: Wells Carrow I. , Vasta James D. , Corona Cesear R. , Wilkinson Jennifer , Zimprich Chad A. , Ingold Morgan R. , Pickett Julie E. , Drewry David H. , Pugh Kathryn M. , Schwinn Marie K. , Hwang Byounghoon , Zegzouti Hicham , Huber Kilian V. M. , Cong Mei , Meisenheimer Poncho L. , Willson Timothy M. , Robers Matthew B. 
Published: June 2020

AbstractConcerted multidisciplinary efforts have led to the development of Cyclin-Dependent Kinase inhibitors (CDKi’s) as small molecule drugs and chemical probes of intracellular CDK function. However, conflicting data has been reported on the inhibitory potency of CDKi’s and a systematic characterization of affinity and selectivity against intracellular CDKs is lacking. We have developed a panel of cell-permeable energy transfer probes to quantify target occupancy for all 21 human CDKs in live cells, and present a comprehensive evaluation of intracellular isozyme potency and selectivity for a collection of 46 clinically-advanced CDKi’s and tool molecules. We observed unexpected intracellular activity profiles for a number of CDKi’s, offering avenues for repurposing of highly potent molecules as probes for previously unreported targets. Overall, we provide a broadly applicable method for evaluating the selectivity of CDK inhibitors in living cells, and present a refined set of tool molecules to study CDK function.
Multistable and dynamic CRISPRi-based synthetic circuits
Authors: Santos-Moreno Javier , Tasiudi Eve , Stelling Joerg , Schaerli Yolanda 
Published: June 2020

AbstractGene expression control based on CRISPRi (clustered regularly interspaced short palindromic repeats interference) has emerged as a powerful tool for creating synthetic gene circuits, both in prokaryotes and in eukaryotes; yet, its lack of cooperativity has been pointed out as a potential obstacle for dynamic or multistable synthetic circuit construction. Here we use CRISPRi to build a synthetic oscillator (“CRISPRlator”), bistable network (toggle switch) and stripe pattern-forming incoherent feed-forward loop (IFFL). Our circuit designs, conceived to feature high predictability and orthogonality, as well as low metabolic burden and context-dependency, allow us to achieve robust circuit behaviors in Escherichia coli populations. Mathematical modeling suggests that unspecific binding in CRISPRi is essential to establish multistability. Our work demonstrates the wide applicability of CRISPRi in synthetic circuits and paves the way for future efforts towards engineering more complex synthetic networks, boosted by the advantages of CRISPR technology.