bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermally robust spin correlations between two 85Rb atoms in an optical microtrap
Authors: Sompet Pimonpan , Szigeti Stuart S. , Schwartz Eyal , Bradley Ashton S. , Andersen Mikkel F. 
Published: April 2019

AbstractThe complex collisional properties of atoms fundamentally limit investigations into a range of processes in many-atom ensembles. In contrast, the bottom-up assembly of few- and many-body systems from individual atoms offers a controlled approach to isolating and studying such collisional processes. Here, we use optical tweezers to individually assemble pairs of trapped 85Rb atoms, and study the spin dynamics of the two-body system in a thermal state. The spin-2 atoms show strong pair correlation between magnetic sublevels on timescales exceeding one second, with measured relative number fluctuations 11.9 ± 0.3 dB below quantum shot noise, limited only by detection efficiency. Spin populations display relaxation dynamics consistent with simulations and theoretical predictions for 85Rb spin interactions, and contrary to the coherent spin waves witnessed in finite-temperature many-body experiments and zero-temperature two-body experiments. Our experimental approach offers a versatile platform for studying two-body quantum dynamics and may provide a route to thermally robust entanglement generation.
The cyclooxygenase-1/mPGES-1/endothelial prostaglandin EP4 receptor pathway constrains myocardial ischemia-reperfusion injury
Authors: Zhu Liyuan , Xu Chuansheng , Huo Xingyu , Hao Huifeng , Wan Qing , Chen Hong , Zhang Xu , Breyer Richard M. , Huang Yu , Cao Xuetao , Liu De-Pei , FitzGerald Garret A. , Wang Miao 
Published: April 2019

AbstractThe use of nonsteroidal anti-inflammatory drugs that inhibit cyclooxygenase (COX)-1 and COX-2, increases heart failure risk. It is unknown whether microsomal (m) prostaglandin (PG) E synthase (S)-1, a target downstream of COX, regulates myocardial (M) ischemia/reperfusion (I/R) injury, a key determinant of heart failure. Here we report that COX-1 and mPGES-1 mediate production of substantial amounts of PGE2 and confer cardiac protection in MI/R. Deletion of mPges-1 impairs cardiac microvascular perfusion and increases inflammatory cell infiltration in mouse MI/R. Consistently, mPges-1 deletion depresses the arteriolar dilatory response to I/R in vivo and to acetylcholine ex vivo, and enhances leukocyte-endothelial cell interaction, which is mediated via PGE receptor-4 (EP4). Furthermore, endothelium-restricted Ep4 deletion impairs microcirculation, and exacerbates MI/R injury, irrespective of EP4 agonism. Treatment with misoprostol, a clinically available PGE analogue, improves microcirculation and reduces MI/R injury. Thus, mPGES-1, a key microcirculation protector, constrains MI/R injury and this beneficial effect is partially mediated via endothelial EP4.
Bacterial chemotaxis in a microfluidic T-maze reveals strong phenotypic heterogeneity in chemotactic sensitivity
Authors: Salek M. Mehdi , Carrara Francesco , Fernandez Vicente , Guasto Jeffrey S. , Stocker Roman 
Published: April 2019

AbstractMany microorganisms have evolved chemotactic strategies to exploit the microscale heterogeneity that frequently characterizes microbial habitats. Chemotaxis has been primarily studied as an average characteristic of a population, with little regard for variability among individuals. Here, we adopt a classic tool from animal ecology – the T-maze – and implement it at the microscale by using microfluidics to expose bacteria to a sequence of decisions, each consisting of migration up or down a chemical gradient. Single-cell observations of clonal Escherichia coli in the maze, coupled with a mathematical model, reveal that strong heterogeneity in the chemotactic sensitivity coefficient exists even within clonal populations of bacteria. A comparison of different potential sources of heterogeneity reveals that heterogeneity in the T-maze originates primarily from the chemotactic sensitivity coefficient, arising from a distribution of pathway gains. This heterogeneity may have a functional role, for example in the context of migratory bet-hedging strategies.
Towards super-clean graphene
Authors: Lin Li , Zhang Jincan , Su Haisheng , Li Jiayu , Sun Luzhao , Wang Zihao , Xu Fan , Liu Chang , Lopatin Sergei , Zhu Yihan , Jia Kaicheng , Chen Shulin , Rui Dingran , Sun Jingyu , Xue Ruiwen , Gao Peng , Kang Ning , Han Yu , Xu H. Q. , Cao Yang , Novoselov K. S. , Tian Zhongqun , Ren Bin , Peng Hailin , Liu Zhongfan 
Published: April 2019

AbstractImpurities produced during the synthesis process of a material pose detrimental impacts upon the intrinsic properties and device performances of the as-obtained product. This effect is especially pronounced in graphene, where surface contamination has long been a critical, unresolved issue, given graphene’s two-dimensionality. Here we report the origins of surface contamination of graphene, which is primarily rooted in chemical vapour deposition production at elevated temperatures, rather than during transfer and storage. In turn, we demonstrate a design of Cu substrate architecture towards the scalable production of super-clean graphene (>99% clean regions). The readily available, super-clean graphene sheets contribute to an enhancement in the optical transparency and thermal conductivity, an exceptionally lower-level of electrical contact resistance and intrinsically hydrophilic nature. This work not only opens up frontiers for graphene growth but also provides exciting opportunities for the utilization of as-obtained super-clean graphene films for advanced applications.
Genome-wide association study of medication-use and associated disease in the UK Biobank
Authors: Wu Yeda , Byrne Enda M. , Zheng Zhili , Kemper Kathryn E. , Yengo Loic , Mallett Andrew J. , Yang Jian , Visscher Peter M. , Wray Naomi R. 
Published: April 2019

AbstractGenome-wide association studies (GWASs) of medication use may contribute to understanding of disease etiology, could generate new leads relevant for drug discovery and can be used to quantify future risk of medication taking. Here, we conduct GWASs of self-reported medication use from 23 medication categories in approximately 320,000 individuals from the UK Biobank. A total of 505 independent genetic loci that meet stringent criteria (P < 10−8/23) for statistical significance are identified. We investigate the implications of these GWAS findings in relation to biological mechanism, potential drug target identification and genetic risk stratification of disease. Amongst the medication-associated genes are 16 known therapeutic-effect target genes for medications from 9 categories. Two of the medication classes studied are for disorders that have not previously been subject to large GWAS (hypothyroidism and gastro-oesophageal reflux disease).
Glutamate spillover in C. elegans triggers repetitive behavior through presynaptic activation of MGL-2/mGluR5
Authors: Katz Menachem , Corson Francis , Keil Wolfgang , Singhal Anupriya , Bae Andrea , Lu Yun , Liang Yupu , Shaham Shai 
Published: April 2019

AbstractGlutamate is a major excitatory neurotransmitter, and impaired glutamate clearance following synaptic release promotes spillover, inducing extra-synaptic signaling. The effects of glutamate spillover on animal behavior and its neural correlates are poorly understood. We developed a glutamate spillover model in Caenorhabditis elegans by inactivating the conserved glial glutamate transporter GLT-1. GLT-1 loss drives aberrant repetitive locomotory reversal behavior through uncontrolled oscillatory release of glutamate onto AVA, a major interneuron governing reversals. Repetitive glutamate release and reversal behavior require the glutamate receptor MGL-2/mGluR5, expressed in RIM and other interneurons presynaptic to AVA. mgl-2 loss blocks oscillations and repetitive behavior; while RIM activation is sufficient to induce repetitive reversals in glt-1 mutants. Repetitive AVA firing and reversals require EGL-30/Gαq, an mGluR5 effector. Our studies reveal that cyclic autocrine presynaptic activation drives repetitive reversals following glutamate spillover. That mammalian GLT1 and mGluR5 are implicated in pathological motor repetition suggests a common mechanism controlling repetitive behaviors.
Sequencing of human genomes with nanopore technology
Authors: Bowden Rory , Davies Robert W. , Heger Andreas , Pagnamenta Alistair T. , de Cesare Mariateresa , Oikkonen Laura E. , Parkes Duncan , Freeman Colin , Dhalla Fatima , Patel Smita Y. , Popitsch Niko , Ip Camilla L. C. , Roberts Hannah E. , Salatino Silvia , Lockstone Helen , Lunter Gerton , Taylor Jenny C. , Buck David , Simpson Michael A. , Donnelly Peter 
Published: April 2019

AbstractWhole-genome sequencing (WGS) is becoming widely used in clinical medicine in diagnostic contexts and to inform treatment choice. Here we evaluate the potential of the Oxford Nanopore Technologies (ONT) MinION long-read sequencer for routine WGS by sequencing the reference sample NA12878 and the genome of an individual with ataxia-pancytopenia syndrome and severe immune dysregulation. We develop and apply a novel reference panel-free analytical method to infer and then exploit phase information which improves single-nucleotide variant (SNV) calling performance from otherwise modest levels. In the clinical sample, we identify and directly phase two non-synonymous de novo variants in SAMD9L, (OMIM #159550) inferring that they lie on the same paternal haplotype. Whilst consensus SNV-calling error rates from ONT data remain substantially higher than those from short-read methods, we demonstrate the substantial benefits of analytical innovation. Ongoing improvements to base-calling and SNV-calling methodology must continue for nanopore sequencing to establish itself as a primary method for clinical WGS.
Electrochemically primed functional redox mediator generator from the decomposition of solid state electrolyte
Authors: Li Matthew , Bai Zhengyu , Li Yejing , Ma Lu , Dai Alvin , Wang Xuefeng , Luo Dan , Wu Tianpin , Liu Ping , Yang Lin , Amine Khalil , Chen Zhongwei , Lu Jun 
Published: April 2019

AbstractRecent works into sulfide-type solid electrolyte materials have attracted much attention among the battery community. Specifically, the oxidative decomposition of phosphorus and sulfur based solid state electrolyte has been considered one of the main hurdles towards practical application. Here we demonstrate that this phenomenon can be leveraged when lithium thiophosphate is applied as an electrochemically “switched-on” functional redox mediator-generator for the activation of commercial bulk lithium sulfide at up to 70 wt.% lithium sulfide electrode content. X-ray adsorption near-edge spectroscopy coupled with electrochemical impedance spectroscopy and Raman indicate a catalytic effect of generated redox mediators on the first charge of lithium sulfide. In contrast to pre-solvated redox mediator species, this design decouples the lithium sulfide activation process from the constraints of low electrolyte content cell operation stemming from pre-solvated redox mediators. Reasonable performance is demonstrated at strict testing conditions.
The future of Southeast Asia’s forests
Authors: Estoque Ronald C. , Ooba Makoto , Avitabile Valerio , Hijioka Yasuaki , DasGupta Rajarshi , Togawa Takuya , Murayama Yuji 
Published: April 2019

AbstractWhile Southeast Asia’s forests play important roles in biodiversity conservation and global carbon (C) balance, the region is also a deforestation hotspot. Here, we consider the five shared socioeconomic pathways (SSPs) to portray a range of plausible futures for the region’s forests, employing a state-of-the-art land change modelling procedure and remotely sensed data. We find that by 2050 under the worst-case scenario, SSP 3 (regional rivalry/a rocky road), the region’s forests would shrink by 5.2 million ha. The region’s aboveground forest carbon stock (AFCS) would decrease by 790 Tg C, 21% of which would be due to old-growth forest loss. Conversely, under the best-case scenario, SSP 1 (sustainability/taking the green road), the region is projected to gain 19.6 million ha of forests and 1651 Tg C of AFCS. The choice of the pathway is thus critical for the future of the region’s forests and their ecosystem functions and services.
Cascaded collimator for atomic beams traveling in planar silicon devices
Authors: Li Chao , Chai Xiao , Wei Bochao , Yang Jeremy , Daruwalla Anosh , Ayazi Farrokh , Raman C. 
Published: April 2019

AbstractMicro- and increasingly, nano-fabrication have enabled the miniaturization of atomic devices, from vapor cells to atom chips for Bose-Einstein condensation. Here we present microfabricated planar devices for thermal atomic beams. Etched microchannels were used to create highly collimated, continuous rubidium atom beams traveling parallel to a silicon wafer surface. Precise, lithographic definition of the guiding channels allowed for shaping and tailoring the velocity distributions in ways not possible using conventional machining. Multiple miniature beams with individually prescribed geometries were created, including collimated, focusing and diverging outputs. A “cascaded” collimator was realized with 40 times greater purity than conventional collimators. These localized, miniature atom beam sources can be a valuable resource for a number of quantum technologies, including atom interferometers, clocks, Rydberg atoms, and hybrid atom-nanophotonic systems, as well as enabling controlled studies of atom-surface interactions at the nanometer scale.
The neural dynamics of hierarchical Bayesian causal inference in multisensory perception
Authors: Rohe Tim , Ehlis Ann-Christine , Noppeney Uta 
Published: April 2019

AbstractTransforming the barrage of sensory signals into a coherent multisensory percept relies on solving the binding problem – deciding whether signals come from a common cause and should be integrated or, instead, segregated. Human observers typically arbitrate between integration and segregation consistent with Bayesian Causal Inference, but the neural mechanisms remain poorly understood. Here, we presented people with audiovisual sequences that varied in the number of flashes and beeps, then combined Bayesian modelling and EEG representational similarity analyses. Our data suggest that the brain initially represents the number of flashes and beeps independently. Later, it computes their numbers by averaging the forced-fusion and segregation estimates weighted by the probabilities of common and independent cause models (i.e. model averaging). Crucially, prestimulus oscillatory alpha power and phase correlate with observers’ prior beliefs about the world’s causal structure that guide their arbitration between sensory integration and segregation.
Physical and functional interaction between A20 and ATG16L1-WD40 domain in the control of intestinal homeostasis
Authors: Slowicka Karolina , Serramito-Gómez Inmaculada , Boada-Romero Emilio , Martens Arne , Sze Mozes , Petta Ioanna , Vikkula Hanna K. , De Rycke Riet , Parthoens Eef , Lippens Saskia , Savvides Savvas N. , Wullaert Andy , Vereecke Lars , Pimentel-Muiños Felipe X. , van Loo Geert 
Published: April 2019

AbstractPrevention of inflammatory bowel disease (IBD) relies on tight control of inflammatory, cell death and autophagic mechanisms, but how these pathways are integrated at the molecular level is still unclear. Here we show that the anti-inflammatory protein A20 and the critical autophagic mediator Atg16l1 physically interact and synergize to regulate the stability of the intestinal epithelial barrier. A proteomic screen using the WD40 domain of ATG16L1 (WDD) identified A20 as a WDD-interacting protein. Loss of A20 and Atg16l1 in mouse intestinal epithelium induces spontaneous IBD-like pathology, as characterized by severe inflammation and increased intestinal epithelial cell death in both small and large intestine. Mechanistically, absence of A20 promotes Atg16l1 accumulation, while elimination of Atg16l1 or expression of WDD-deficient Atg16l1 stabilizes A20. Collectively our data show that A20 and Atg16l1 cooperatively control intestinal homeostasis by acting at the intersection of inflammatory, autophagy and cell death pathways.
Single-cell trajectories reconstruction, exploration and mapping of omics data with STREAM
Authors: Chen Huidong , Albergante Luca , Hsu Jonathan Y. , Lareau Caleb A. , Lo Bosco Giosuè , Guan Jihong , Zhou Shuigeng , Gorban Alexander N. , Bauer Daniel E. , Aryee Martin J. , Langenau David M. , Zinovyev Andrei , Buenrostro Jason D. , Yuan Guo-Cheng , Pinello Luca 
Published: April 2019

AbstractSingle-cell transcriptomic assays have enabled the de novo reconstruction of lineage differentiation trajectories, along with the characterization of cellular heterogeneity and state transitions. Several methods have been developed for reconstructing developmental trajectories from single-cell transcriptomic data, but efforts on analyzing single-cell epigenomic data and on trajectory visualization remain limited. Here we present STREAM, an interactive pipeline capable of disentangling and visualizing complex branching trajectories from both single-cell transcriptomic and epigenomic data. We have tested STREAM on several synthetic and real datasets generated with different single-cell technologies. We further demonstrate its utility for understanding myoblast differentiation and disentangling known heterogeneity in hematopoiesis for different organisms. STREAM is an open-source software package.
Multifunctional CRISPR-Cas9 with engineered immunosilenced human T cell epitopes
Authors: Ferdosi Shayesteh R. , Ewaisha Radwa , Moghadam Farzaneh , Krishna Sri , Park Jin G. , Ebrahimkhani Mo R. , Kiani Samira , Anderson Karen S. 
Published: April 2019

AbstractThe CRISPR-Cas9 system has raised hopes for developing personalized gene therapies for complex diseases. Its application for genetic and epigenetic therapies in humans raises concerns over immunogenicity of the bacterially derived Cas9 protein. Here we detect antibodies to Streptococcus pyogenes Cas9 (SpCas9) in at least 5% of 143 healthy individuals. We also report pre-existing human CD8+T cell immunity in the majority of healthy individuals screened. We identify two immunodominant SpCas9 T cell epitopes for HLA-A*02:01 using an enhanced prediction algorithm that incorporates T cell receptor contact residue hydrophobicity and HLA binding and evaluated them by T cell assays using healthy donor PBMCs. In a proof-of-principle study, we demonstrate that Cas9 protein can be modified to eliminate immunodominant epitopes through targeted mutation while preserving its function and specificity. Our study highlights the problem of pre-existing immunity against CRISPR-associated nucleases and offers a potential solution to mitigate the T cell immune response.
Metabolic profiling of cancer cells reveals genome-wide crosstalk between transcriptional regulators and metabolism
Authors: Ortmayr Karin , Dubuis Sébastien , Zampieri Mattia 
Published: April 2019

AbstractTranscriptional reprogramming of cellular metabolism is a hallmark of cancer. However, systematic approaches to study the role of transcriptional regulators (TRs) in mediating cancer metabolic rewiring are missing. Here, we chart a genome-scale map of TR-metabolite associations in human cells using a combined computational-experimental framework for large-scale metabolic profiling of adherent cell lines. By integrating intracellular metabolic profiles of 54 cancer cell lines with transcriptomic and proteomic data, we unraveled a large space of associations between TRs and metabolic pathways. We found a global regulatory signature coordinating glucose- and one-carbon metabolism, suggesting that regulation of carbon metabolism in cancer may be more diverse and flexible than previously appreciated. Here, we demonstrate how this TR-metabolite map can serve as a resource to predict TRs potentially responsible for metabolic transformation in patient-derived tumor samples, opening new opportunities in understanding disease etiology, selecting therapeutic treatments and in designing modulators of cancer-related TRs.
Dynamic fibroblast contractions attract remote macrophages in fibrillar collagen matrix
Authors: Pakshir Pardis , Alizadehgiashi Moien , Wong Boaz , Coelho Nuno Miranda , Chen Xingyu , Gong Ze , Shenoy Vivek B. , McCulloch Christopher A. , Hinz Boris 
Published: April 2019

AbstractMacrophage (Mϕ)-fibroblast interactions coordinate tissue repair after injury whereas miscommunications can result in pathological healing and fibrosis. We show that contracting fibroblasts generate deformation fields in fibrillar collagen matrix that provide far-reaching physical cues for Mϕ. Within collagen deformation fields created by fibroblasts or actuated microneedles, Mϕ migrate towards the force source from several hundreds of micrometers away. The presence of a dynamic force source in the matrix is critical to initiate and direct Mϕ migration. In contrast, collagen condensation and fiber alignment resulting from fibroblast remodelling activities or chemotactic signals are neither required nor sufficient to guide Mϕ migration. Binding of α2β1 integrin and stretch-activated channels mediate Mϕ migration and mechanosensing in fibrillar collagen ECM. We propose that Mϕ mechanosense the velocity of local displacements of their substrate, allowing contractile fibroblasts to attract Mϕ over distances that exceed the range of chemotactic gradients.
Excessive miR-25-3p maturation via N6-methyladenosine stimulated by cigarette smoke promotes pancreatic cancer progression
Authors: Zhang Jialiang , Bai Ruihong , Li Mei , Ye Huilin , Wu Chen , Wang Chengfeng , Li Shengping , Tan Liping , Mai Dongmei , Li Guolin , Pan Ling , Zheng Yanfen , Su Jiachun , Ye Ying , Fu Zhiqiang , Zheng Shangyou , Zuo Zhixiang , Liu Zexian , Zhao Qi , Che Xu , Xie Dan , Jia Weihua , Zeng Mu-Sheng , Tan Wen , Chen Rufu , Xu Rui-Hua , Zheng Jian , Lin Dongxin 
Published: April 2019

AbstractN6-methyladenosine (m6A) modification is an important mechanism in miRNA processing and maturation, but the role of its aberrant regulation in human diseases remained unclear. Here, we demonstrate that oncogenic primary microRNA-25 (miR-25) in pancreatic duct epithelial cells can be excessively maturated by cigarette smoke condensate (CSC) via enhanced m6A modification that is mediated by NF-κB associated protein (NKAP). This modification is catalyzed by overexpressed methyltransferase-like 3 (METTL3) due to hypomethylation of theMETTL3promoter also caused by CSC. Mature miR-25, miR-25-3p, suppresses PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2), resulting in the activation of oncogenic AKT-p70S6K signaling, which provokes malignant phenotypes of pancreatic cancer cells. High levels of miR-25-3p are detected in smokers and in pancreatic cancers tissues that are correlated with poor prognosis of pancreatic cancer patients. These results collectively indicate that cigarette smoke-induced miR-25-3p excessive maturation via m6A modification promotes the development and progression of pancreatic cancer.