bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large‐Scale Industrial Cloud Perturbations Confirm Bidirectional Cloud Water Responses to Anthropogenic Aerosols
Authors: Trofimov Heido , Bellouin Nicolas , Toll Velle 
Published: June 2020

AbstractAerosols offset a poorly quantified fraction of anthropogenic greenhouse gas warming, and the aerosol impact on clouds is the most uncertain mechanism of anthropogenic climate forcing. Here observations of a relatively weak average response of liquid cloud water to aerosol perturbations are extended to much larger areas than in previous studies, with the polluted cloud areas covering hundreds by hundreds of kilometers. Polluted clouds detected in satellite images at the global anthropogenic air pollution hot spot of Norilsk, Russia, and at other various major aerosol source regions show close compensation between aerosol‐induced cloud water increases and decreases. In the sampled Norilsk cloud perturbations the decrease in liquid water path offsets 3% of the radiative forcing through the Twomey effect on average. Weak cloud water response on average in large polluted areas is in very good agreement with previous results based on observations of small‐scale ship‐track‐like industrial cloud perturbations, helping to reduce the uncertainty associated with the anthropogenic aerosol impacts on clouds.
Geomagnetically Induced Current Model Validation From New Zealand's South Island
Authors: Divett T. , Mac Manus D. H. , Richardson G. S. , Beggan C. D. , Rodger C. J. , Ingham M. , Clarke E. , Thomson A. W. P. , Dalzell M. , Obana Y. 
Published: June 2020

AbstractGeomagnetically induced currents (GICs) during a space weather event have previously caused transformer damage in New Zealand. During the 2015 St. Patrick's Day Storm, Transpower NZ Ltd has reliable GIC measurements at 23 different transformers across New Zealand's South Island. These observed GICs show large variability, spatially and within a substation. We compare these GICs with those calculated from a modeled geolectric field using a network model of the transmission network with industry‐provided line, earthing, and transformer resistances. We calculate the modeled geoelectric field from the spectra of magnetic field variations interpolated from measurements during this storm and ground conductance using a thin‐sheet model. Modeled and observed GIC spectra are similar, and coherence exceeds the 95% confidence threshold, for most valid frequencies at 18 of the 23 transformers. Sensitivity analysis shows that modeled GICs are most sensitive to variation in magnetic field input, followed by the variation in land conductivity. The assumption that transmission lines follow straight lines or getting the network resistances exactly right is less significant. Comparing modeled and measured GIC time series highlights that this modeling approach is useful for reconstructing the timing, duration, and relative magnitude of GIC peaks during sudden commencement and substorms. However, the model significantly underestimates the magnitude of these peaks, even for a transformer with good spectral match. This is because of the limited range of frequencies for which the thin‐sheet model is valid and severely limits the usefulness of this modeling approach for accurate prediction of peak GICs.
Precision weighting of cortical unsigned prediction error signals benefits learning, is mediated by dopamine, and is impaired in psychosis
Authors: Haarsma J. , Fletcher P. C. , Griffin J. D. , Taverne H. J. , Ziauddeen H. , Spencer T. J. , Miller C. , Katthagen T. , Goodyer I. , Diederen K. M. J. , Murray G. K. 
Published: June 2020

AbstractRecent theories of cortical function construe the brain as performing hierarchical Bayesian inference. According to these theories, the precision of prediction errors plays a key role in learning and decision-making, is controlled by dopamine and contributes to the pathogenesis of psychosis. To test these hypotheses, we studied learning with variable outcome-precision in healthy individuals after dopaminergic modulation with a placebo, a dopamine receptor agonist bromocriptine or a dopamine receptor antagonist sulpiride (dopamine study n = 59) and in patients with early psychosis (psychosis study n = 74: 20 participants with first-episode psychosis, 30 healthy controls and 24 participants with at-risk mental state attenuated psychotic symptoms). Behavioural computational modelling indicated that precision weighting of prediction errors benefits learning in health and is impaired in psychosis. FMRI revealed coding of unsigned prediction errors, which signal surprise, relative to their precision in superior frontal cortex (replicated across studies, combined n = 133), which was perturbed by dopaminergic modulation, impaired in psychosis and associated with task performance and schizotypy (schizotypy correlation in 86 healthy volunteers). In contrast to our previous work, we did not observe significant precision-weighting of signed prediction errors, which signal valence, in the midbrain and ventral striatum in the healthy controls (or patients) in the psychosis study. We conclude that healthy people, but not patients with first-episode psychosis, take into account the precision of the environment when updating beliefs. Precision weighting of cortical prediction error signals is a key mechanism through which dopamine modulates inference and contributes to the pathogenesis of psychosis.
New insights into the distributions of nitrogen fixation and diazotrophs revealed by high-resolution sensing and sampling methods
Authors: Tang Weiyi , Cerdán-García Elena , Berthelot Hugo , Polyviou Despo , Wang Seaver , Baylay Alison , Whitby Hannah , Planquette Hélène , Mowlem Matthew , Robidart Julie , Cassar Nicolas 
Published: June 2020

Abstract
Nitrogen availability limits marine productivity across large ocean regions. Diazotrophs can supply new nitrogen to the marine environment via nitrogen (N2) fixation, relieving nitrogen limitation. The distributions of diazotrophs and N2 fixation have been hypothesized to be generally controlled by temperature, phosphorus, and iron availability in the global ocean. However, even in the North Atlantic where most research on diazotrophs and N2 fixation has taken place, environmental controls remain contentious. Here we measure diazotroph composition, abundance, and activity at high resolution using newly developed underway sampling and sensing techniques. We capture a diazotrophic community shift from Trichodesmium to UCYN-A between the oligotrophic, warm (25–29 °C) Sargasso Sea and relatively nutrient-enriched, cold (13–24 °C) subpolar and eastern American coastal waters. Meanwhile, N2 fixation rates measured in this study are among the highest ever recorded globally and show significant increase with phosphorus availability across the transition from the Gulf Stream into subpolar and coastal waters despite colder temperatures and higher nitrate concentrations. Transcriptional patterns in both Trichodesmium and UCYN-A indicate phosphorus stress in the subtropical gyre. Over this iron-replete transect spanning the western North Atlantic, our results suggest that temperature is the major factor controlling the diazotrophic community structure while phosphorous drives N2 fixation rates. Overall, the occurrence of record-high UCYN-A abundance and peak N2 fixation rates in the cold coastal region where nitrate concentrations are highest (~200 nM) challenges current paradigms on what drives the distribution of diazotrophs and N2 fixation.
Enalapril overcomes chemoresistance and potentiates antitumor efficacy of 5-FU in colorectal cancer by suppressing proliferation, angiogenesis, and NF-κB/STAT3-regulated proteins
Authors: Yang Yushan , Ma Lulu , Xu Yiming , Liu Yun , Li Wenya , Cai Jianchun , Zhang Yiyao 
Published: June 2020

Abstract5-Fluorouracil (5-FU) is one of the most effective drugs for the treatment of colorectal cancer (CRC). However, there is an urgent need in reducing its systemic side effects and chemoresistance to make 5-FU-based chemotherapy more effective and less toxic in the treatment of CRC. Here, enalapril, a clinically widely used antihypertensive and anti-heart failure drug, has been verified as a chemosensitizer that extremely improves the sensitivity of CRC cells to 5-FU. Enalapril greatly augmented the cytotoxicity of 5-FU on the cell growth in both established and primary CRC cells. The combination of enalapril and 5-FU synergistically suppressed the cell migration and invasion in both 5-FU-sensitive and -resistant CRC cells in vitro, and inhibited angiogenesis, tumor growth, and metastasis of 5-FU-resistant CRC cells in vivo without increased systemic toxicity at concentrations that were ineffective as individual agents. Furthermore, combined treatment cooperatively inhibited NF-κB/STAT3 signaling pathway and subsequently reduced the expression levels of NF-κB/STAT3-regulated proteins (c-Myc, Cyclin D1, MMP-9, MMP-2, VEGF, Bcl-2, and XIAP) in vitro and in vivo. This study provides the first evidence that enalapril greatly sensitized CRC cells to 5-FU at clinically achievable concentrations without additional toxicity and the synergistic effect may be mainly by cooperatively suppressing proliferation, angiogenesis, and NF-κB/STAT3-regulated proteins.
Chronic circadian disruption modulates breast cancer stemness and immune microenvironment to drive metastasis in mice
Authors: Hadadi Eva , Taylor William , Li Xiao-Mei , Aslan Yetki , Villote Marthe , Rivière Julie , Duvallet Gaelle , Auriau Charlotte , Dulong Sandrine , Raymond-Letron Isabelle , Provot Sylvain , Bennaceur-Griscelli Annelise , Acloque Hervé 
Published: June 2020

AbstractBreast cancer is the most common type of cancer worldwide and one of the major causes of cancer death in women. Epidemiological studies have established a link between night-shift work and increased cancer risk, suggesting that circadian disruption may play a role in carcinogenesis. Here, we aim to shed light on the effect of chronic jetlag (JL) on mammary tumour development. To do this, we use a mouse model of spontaneous mammary tumourigenesis and subject it to chronic circadian disruption. We observe that circadian disruption significantly increases cancer-cell dissemination and lung metastasis. It also enhances the stemness and tumour-initiating potential of tumour cells and creates an immunosuppressive shift in the tumour microenvironment. Finally, our results suggest that the use of a CXCR2 inhibitor could correct the effect of JL on cancer-cell dissemination and metastasis. Altogether, our data provide a conceptual framework to better understand and manage the effects of chronic circadian disruption on breast cancer progression.
Structural plasticity of SARS-CoV-2 3CL Mpro active site cavity revealed by room temperature X-ray crystallography
Authors: Kneller Daniel W. , Phillips Gwyndalyn , O’Neill Hugh M. , Jedrzejczak Robert , Stols Lucy , Langan Paul , Joachimiak Andrzej , Coates Leighton , Kovalevsky Andrey 
Published: June 2020

AbstractThe COVID-19 disease caused by the SARS-CoV-2 coronavirus has become a pandemic health crisis. An attractive target for antiviral inhibitors is the main protease 3CL Mpro due to its essential role in processing the polyproteins translated from viral RNA. Here we report the room temperature X-ray structure of unliganded SARS-CoV-2 3CL Mpro, revealing the ligand-free structure of the active site and the conformation of the catalytic site cavity at near-physiological temperature. Comparison with previously reported low-temperature ligand-free and inhibitor-bound structures suggest that the room temperature structure may provide more relevant information at physiological temperatures for aiding in molecular docking studies.
Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development
Authors: Yagi Masaki , Kabata Mio , Tanaka Akito , Ukai Tomoyo , Ohta Sho , Nakabayashi Kazuhiko , Shimizu Masahito , Hata Kenichiro , Meissner Alexander , Yamamoto Takuya , Yamada Yasuhiro 
Published: June 2020

AbstractDe novo establishment of DNA methylation is accomplished by DNMT3A and DNMT3B. Here, we analyze de novo DNA methylation in mouse embryonic fibroblasts (2i-MEFs) derived from DNA-hypomethylated 2i/L ES cells with genetic ablation of Dnmt3a or Dnmt3b. We identify 355 and 333 uniquely unmethylated genes in Dnmt3a and Dnmt3b knockout (KO) 2i-MEFs, respectively. We find that Dnmt3a is exclusively required for de novo methylation at both TSS regions and gene bodies of Polycomb group (PcG) target developmental genes, while Dnmt3b has a dominant role on the X chromosome. Consistent with this, tissue-specific DNA methylation at PcG target genes is substantially reduced in Dnmt3a KO embryos. Finally, we find that human patients with DNMT3 mutations exhibit reduced DNA methylation at regions that are hypomethylated in Dnmt3 KO 2i-MEFs. In conclusion, here we report a set of unique de novo DNA methylation target sites for both DNMT3 enzymes during mammalian development that overlap with hypomethylated sites in human patients.
Oncolytic virus-derived type I interferon restricts CAR T cell therapy
Authors: Evgin Laura , Huff Amanda L. , Wongthida Phonphimon , Thompson Jill , Kottke Tim , Tonne Jason , Schuelke Matthew , Ayasoufi Katayoun , Driscoll Christopher B. , Shim Kevin G. , Reynolds Pierce , Monie Dileep D. , Johnson Aaron J. , Coffey Matt , Young Sarah L. , Archer Gary , Sampson John , Pulido Jose , Perez Luis Sanchez , Vile Richard 
Published: June 2020

AbstractThe application of adoptive T cell therapies, including those using chimeric antigen receptor (CAR)-modified T cells, to solid tumors requires combinatorial strategies to overcome immune suppression associated with the tumor microenvironment. Here we test whether the inflammatory nature of oncolytic viruses and their ability to remodel the tumor microenvironment may help to recruit and potentiate the functionality of CAR T cells. Contrary to our hypothesis, VSVmIFNβ infection is associated with attrition of murine EGFRvIII CAR T cells in a B16EGFRvIII model, despite inducing a robust proinflammatory shift in the chemokine profile. Mechanistically, type I interferon (IFN) expressed following infection promotes apoptosis, activation, and inhibitory receptor expression, and interferon-insensitive CAR T cells enable combinatorial therapy with VSVmIFNβ. Our study uncovers an unexpected mechanism of therapeutic interference, and prompts further investigation into the interaction between CAR T cells and oncolytic viruses to optimize combination therapy.
Single-atom Ni-N4 provides a robust cellular NO sensor
Authors: Zhou Min , Jiang Ying , Wang Guo , Wu Wenjie , Chen Wenxing , Yu Ping , Lin Yuqing , Mao Junjie , Mao Lanqun 
Published: June 2020

AbstractNitric oxide (NO) has been implicated in a variety of physiological and pathological processes. Monitoring cellular levels of NO requires a sensor to feature adequate sensitivity, transient recording ability and biocompatibility. Herein we report a single-atom catalysts (SACs)-based electrochemical sensor for the detection of NO in live cellular environment. The system employs nickel single atoms anchored on N-doped hollow carbon spheres (Ni SACs/N-C) that act as an excellent catalyst for electrochemical oxidation of NO. Notably, Ni SACs/N-C shows superior electrocatalytic performance to the commonly used Ni based nanomaterials, attributing from the greatly reduced Gibbs free energy that are required for Ni SACs/N-C in activating NO oxidation. Moreover, Ni SACs-based flexible and stretchable sensor shows high biocompatibility and low nanomolar sensitivity, enabling the real-time monitoring of NO release from cells upon drug and stretch stimulation. Our results demonstrate a promising means of using SACs for electrochemical sensing applications.
Fast and sensitive flow-injection mass spectrometry metabolomics by analyzing sample-specific ion distributions
Authors: Sarvin Boris , Lagziel Shoval , Sarvin Nikita , Mukha Dzmitry , Kumar Praveen , Aizenshtein Elina , Shlomi Tomer 
Published: June 2020

AbstractMass spectrometry based metabolomics is a widely used approach in biomedical research. However, current methods coupling mass spectrometry with chromatography are time-consuming and not suitable for high-throughput analysis of thousands of samples. An alternative approach is flow-injection mass spectrometry (FI-MS) in which samples are directly injected to the ionization source. Here, we show that the sensitivity of Orbitrap FI-MS metabolomics methods is limited by ion competition effect. We describe an approach for overcoming this effect by analyzing the distribution of ion m/z values and computationally determining a series of optimal scan ranges. This enables reproducible detection of ~9,000 and ~10,000 m/z features in metabolomics and lipidomics analysis of serum samples, respectively, with a sample scan time of ~15 s and duty time of ~30 s; a ~50% increase versus current spectral-stitching FI-MS. This approach facilitates high-throughput metabolomics for a variety of applications, including biomarker discovery and functional genomics screens.
Streptococcus mutans adhesion force sensing in multi-species oral biofilms
Authors: Wang Can , van der Mei Henny C. , Busscher Henk J. , Ren Yijin 
Published: June 2020

AbstractBacteria utilize chemical and mechanical mechanisms to sense their environment, to survive hostile conditions. In mechanical sensing, intra-bilayer pressure profiles change due to deformation induced by the adhesion forces bacteria experience on a surface. Emergent properties in mono-species Streptococcus mutans biofilms, such as extracellular matrix production, depend on the adhesion forces that streptococci sense. Here we determined whether and how salivary-conditioning film (SCF) adsorption and the multi-species nature of oral biofilm influence adhesion force sensing and associated gene expression by S. mutans. Hereto, Streptococcus oralis, Actinomyces naeslundii, and S. mutans were grown together on different surfaces in the absence and presence of an adsorbed SCF. Atomic force microscopy and RT-qPCR were used to measure S. mutans adhesion forces and gene expressions. Upon SCF adsorption, stationary adhesion forces decreased on a hydrophobic and increased on a hydrophilic surface to around 8 nN. Optical coherence tomography showed that triple-species biofilms on SCF-coated surfaces with dead S. oralis adhered weakly and often detached as a contiguous sheet. Concurrently, S. mutans displayed no differential adhesion force sensing on SCF-coated surfaces in the triple-species biofilms with dead S. oralis, but once live S. oralis were present S. mutans adhesion force sensing and gene expression ranked similar as on surfaces in the absence of an adsorbed SCF. Concluding, live S. oralis may enzymatically degrade SCF components to facilitate direct contact of biofilm inhabitants with surfaces and allow S. mutans adhesion force sensing of underlying surfaces to define its appropriate adaptive response. This represents a new function of initial colonizers in multi-species oral biofilms.
RNA sequencing analysis of the human retina and associated ocular tissues
Authors: Schumacker Scott T. , Coppage Krista R. , Enke Ray A. 
Published: June 2020

AbstractThe retina is a stratified layer of sensory neurons lining the posterior portion of the eye. In humans, fine detail and color vision are enabled by the macula, a central region of the retina dense in cone photoreceptors (PRs). Achromatic low light and peripheral vision are facilitated by rod PRs found with increasing density outside the macula in the peripheral retina. The outer retina is nourished by choroidal blood flow regulated by a single layer of intervening retinal pigment epithelial (RPE) cells. Existing human retinal transcriptome projects have been critical for studying aspects of retinal development and disease however, there are currently no publicly available data sets accurately describing the aging human central retina, peripheral retina, and supporting RPE/choroid. Here we used Illumina RNA sequencing (RNA-seq) analysis to characterize the mRNA transcriptome of rod and cone PR-enriched human retina as well as supporting macular RPE/choroid tissue. These data will be valuable to the vision research community for characterizing global changes in gene expression in clinically relevant ocular tissues.
Vortex phases and glassy dynamics in the highly anisotropic superconductor HgBa2CuO4+δ
Authors: Eley Serena , Willa Roland , Chan Mun K. , Bauer Eric D. , Civale Leonardo 
Published: June 2020

AbstractWe present an extensive study of vortex dynamics in a high-quality single crystal of HgBa2CuO4+δ, a highly anisotropic superconductor that is a model system for studying the effects of anisotropy. From magnetization M measurements over a wide range of temperatures T and fields H, we construct a detailed vortex phase diagram. We find that the temperature-dependent vortex penetration field Hp(T), second magnetization peak Hsmp(T), and irreversibility field Hirr(T) all decay exponentially at low temperatures and exhibit an abrupt change in behavior at high temperatures T/Tc >~ 0.5. By measuring the rates of thermally activated vortex motion (creep) S(T, H) = |dlnM(T, H)/dlnt|, we reveal glassy behavior involving collective creep of bundles of 2D pancake vortices as well as temperature- and time-tuned crossovers from elastic (collective) dynamics to plastic flow. Based on the creep results, we show that the second magnetization peak coincides with the elastic-to-plastic crossover at low T, yet the mechanism changes at higher temperatures.