bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heritability estimates for 361 blood metabolites across 40 genome-wide association studies
Authors: Hagenbeek Fiona A. , Pool René , van Dongen Jenny , Draisma Harmen H. M. , Jan Hottenga Jouke , Willemsen Gonneke , Abdellaoui Abdel , Fedko Iryna O. , den Braber Anouk , Visser Pieter Jelle , de Geus Eco J. C. N. , Willems van Dijk Ko , Verhoeven Aswin , Suchiman H. Eka , Beekman Marian , Slagboom P. Eline , van Duijn Cornelia M. ,   BBMRI Metabolomics Consortium, Barkey Wolf J. J. H. , Cats D. , Amin N. , Beulens J. W. , van der Bom J. A. , Bomer N. , Demirkan A. , van Hilten J. A. , Meessen J. M. T. A. , Moed M. H. , Fu J. , Onderwater G. L. J. , Rutters F. , So-Osman C. , van der Flier W. M. , van der Heijden A. A. W. A. , van der Spek A. , Asselbergs F. W. , Boersma E. , Elders P. M. , Geleijnse J. M. , Ikram M. A. , Kloppenburg M. , Meulenbelt I. , Mooijaart S. P. , Nelissen R. G. H. H. , Netea M. G. , Penninx B. W. J. H. , Stehouwer C. D. A. , Teunissen C. E. , Terwindt G. M. , ‘t Hart L. M. , van den Maagdenberg A. M. J. M. , van der Harst P. , van der Horst I. C. C. , van der Kallen C. J. H. , van Greevenbroek M. M. J. , van Spil W. E. , Wijmenga C. , Zwinderman A. H. , Zhernikova A. , Jukema J. W. , Mei H. , Slofstra M. , Swertz M. , van den Akker E. B. , Deelen J. , Reinders M. J. T. , Harms Amy C. , Hankemeier Thomas , Bartels Meike , Nivard Michel G. , Boomsma Dorret I. 
Published: January 2020

AbstractMetabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2total), and the proportion of heritability captured by known metabolite loci (h2Metabolite-hits) for 309 lipids and 52 organic acids. Our study reveals significant differences in h2Metabolite-hitsamong different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h2Metabolite-hitsestimates than phosphatidylcholines with low degrees of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes.
Quantitative earthquake-like statistical properties of the flow of soft materials below yield stress
Authors: Bera P. K. , Majumdar S. , Ouillon G. , Sornette D. , Sood A. K. 
Published: January 2020

AbstractThe flow behavior of soft materials below the yield stress can be rich and is not fully understood. Here, we report shear-stress-induced reorganization of three-dimensional solid-like soft materials formed by closely packed nematic domains of surfactant micelles and a repulsive Wigner glass formed by anisotropic clay nano-discs having ionic interactions. The creep response of both the systems below the yield stress results in angular velocity fluctuations of the shearing plate showing large temporal burst-like events that resemble seismic foreshocks-aftershocks data measuring the ground motion during earthquake avalanches. We find that the statistical properties of the quake events inside such a burst map on to the scaling relations for magnitude and frequency distribution of earthquakes, given by Gutenberg-Richter and Omori laws, and follow a power-law distribution of the inter-occurrence waiting time. In situ polarized optical microscopy reveals that during these events the system self-organizes to a much stronger solid-like state.
Microparticle traction force microscopy reveals subcellular force exertion patterns in immune cell–target interactions
Authors: Vorselen Daan , Wang Yifan , de Jesus Miguel M. , Shah Pavak K. , Footer Matthew J. , Huse Morgan , Cai Wei , Theriot Julie A. 
Published: January 2020

AbstractForce exertion is an integral part of cellular behavior. Traction force microscopy (TFM) has been instrumental for studying such forces, providing spatial force measurements at subcellular resolution. However, the applications of classical TFM are restricted by the typical planar geometry. Here, we develop a particle-based force sensing strategy for studying cellular interactions. We establish a straightforward batch approach for synthesizing uniform, deformable and tuneable hydrogel particles, which can also be easily derivatized. The 3D shape of such particles can be resolved with superresolution (<50 nm) accuracy using conventional confocal microscopy. We introduce a reference-free computational method allowing inference of traction forces with high sensitivity directly from the particle shape. We illustrate the potential of this approach by revealing subcellular force patterns throughout phagocytic engulfment and force dynamics in the cytotoxic T-cell immunological synapse. This strategy can readily be adapted for studying cellular forces in a wide range of applications.
Electrooxidation enables highly regioselective dearomative annulation of indole and benzofuran derivatives
Authors: Liu Kun , Song Wenxu , Deng Yuqi , Yang Huiyue , Song Chunlan , Abdelilah Takfaoui , Wang Shengchun , Cong Hengjiang , Tang Shan , Lei Aiwen 
Published: January 2020

AbstractThe dearomatization of arenes represents a powerful synthetic methodology to provide three-dimensional chemicals of high added value. Here we report a general and practical protocol for regioselective dearomative annulation of indole and benzofuran derivatives in an electrochemical way. Under undivided electrolytic conditions, a series of highly functionalized five to eight-membered heterocycle-2,3-fused indolines and dihydrobenzofurans, which are typically unattainable under thermal conditions, can be successfully accessed in high yield with excellent regio- and stereo-selectivity. This transformation can also tolerate a wide range of functional groups and achieve good efficiency in large-scale synthesis under oxidant-free conditions. In addition, cyclic voltammetry, electron paramagnetic resonance (EPR) and kinetic studies indicate that the dehydrogenative dearomatization annulations arise from the anodic oxidation of indole into indole radical cation, and this process is the rate-determining step.
The Mouse Gut Microbial Biobank expands the coverage of cultured bacteria
Authors: Liu Chang , Zhou Nan , Du Meng-Xuan , Sun Yu-Tong , Wang Kai , Wang Yu-Jing , Li Dan-Hua , Yu Hai-Ying , Song Yuqin , Bai Bing-Bing , Xin Yuhua , Wu Linhuan , Jiang Cheng-Ying , Feng Jie , Xiang Hua , Zhou Yuguang , Ma Juncai , Wang Jun , Liu Hong-Wei , Liu Shuang-Jiang 
Published: January 2020

AbstractMice are widely used as experimental models for gut microbiome (GM) studies, yet the majority of mouse GM members remain uncharacterized. Here, we report the construction of a mouse gut microbial biobank (mGMB) that contains 126 species, represented by 244 strains that have been deposited in the China General Microorganism Culture Collection. We sequence and phenotypically characterize 77 potential new species and propose their nomenclatures. The mGMB includes 22 and 17 species that are significantly enriched in ob/ob and wild-type C57BL/6J mouse cecal samples, respectively. The genomes of the 126 species in the mGMB cover 52% of the metagenomic nonredundant gene catalog (sequence identity ≥ 60%) and represent 93–95% of the KEGG-Orthology-annotated functions of the sampled mouse GMs. The microbial and genome data assembled in the mGMB enlarges the taxonomic characterization of mouse GMs and represents a useful resource for studies of host-microbe interactions and of GM functions associated with host health and diseases.
Quantitative live cell imaging reveals influenza virus manipulation of Rab11A transport through reduced dynein association
Authors: Bhagwat Amar R. , Le Sage Valerie , Nturibi Eric , Kulej Katarzyna , Jones Jennifer , Guo Min , Tae Kim Eui , Garcia Benjamin A. , Weitzman Matthew D. , Shroff Hari , Lakdawala Seema S. 
Published: January 2020

AbstractAssembly of infectious influenza A viruses (IAV) is a complex process involving transport from the nucleus to the plasma membrane. Rab11A-containing recycling endosomes have been identified as a platform for intracellular transport of viral RNA (vRNA). Here, using high spatiotemporal resolution light-sheet microscopy (~1.4 volumes/second, 330 nm isotropic resolution), we quantify Rab11A and vRNA movement in live cells during IAV infection and report that IAV infection decreases speed and increases arrest of Rab11A. Unexpectedly, infection with respiratory syncytial virus alters Rab11A motion in a manner opposite to IAV, suggesting that Rab11A is a common host component that is differentially manipulated by respiratory RNA viruses. Using two-color imaging we demonstrate co-transport of Rab11A and IAV vRNA in infected cells and provide direct evidence that vRNA-associated Rab11A have altered transport. The mechanism of altered Rab11A movement is likely related to a decrease in dynein motors bound to Rab11A vesicles during IAV infection.
BCL9 provides multi-cellular communication properties in colorectal cancer by interacting with paraspeckle proteins
Authors: Jiang Meng , Kang Yue , Sewastianik Tomasz , Wang Jiao , Tanton Helen , Alder Keith , Dennis Peter , Xin Yu , Wang Zhongqiu , Liu Ruiyang , Zhang Mengyun , Huang Ying , Loda Massimo , Srivastava Amitabh , Chen Runsheng , Liu Ming , Carrasco Ruben D. 
Published: January 2020

AbstractColorectal cancer (CRC) is the third most commonly diagnosed cancer, which despite recent advances in treatment, remains incurable due to molecular heterogeneity of tumor cells. The B-cell lymphoma 9 (BCL9) oncogene functions as a transcriptional co-activator of the Wnt/β-catenin pathway, which plays critical roles in CRC pathogenesis. Here we have identified a β-catenin-independent function of BCL9 in a poor-prognosis subtype of CRC tumors characterized by expression of stromal and neural associated genes. In response to spontaneous calcium transients or cellular stress, BCL9 is recruited adjacent to the interchromosomal regions, where it stabilizes the mRNA of calcium signaling and neural associated genes by interacting with paraspeckle proteins. BCL9 subsequently promotes tumor progression and remodeling of the tumor microenvironment (TME) by sustaining the calcium transients and neurotransmitter-dependent communication among CRC cells. These data provide additional insights into the role of BCL9 in tumor pathogenesis and point towards additional avenues for therapeutic intervention.
Imaging of fluorescence anisotropy during photoswitching provides a simple readout for protein self-association
Authors: Ojha Namrata , Rainey Kristin H. , Patterson George H. 
Published: January 2020

AbstractMonitoring of protein oligomerization has benefited greatly from Förster Resonance Energy Transfer (FRET) measurements. Although donors and acceptors are typically fluorescent molecules with different spectra, homo-FRET can occur between fluorescent molecules of the same type if the emission spectrum overlaps with the absorption spectrum. Here, we describe homo-FRET measurements by monitoring anisotropy changes in photoswitchable fluorescent proteins while photoswitching to the off state. These offer the capability to estimate anisotropy in the same specimen during homo-FRET as well as non-FRET conditions. We demonstrate photoswitching anisotropy FRET (psAFRET) with a number of test chimeras and example oligomeric complexes inside living cells. We also present an equation derived from FRET and anisotropy equations which converts anisotropy changes into a factor we call delta r FRET (drFRET). This is analogous to an energy transfer efficiency and allows experiments performed on a given homo-FRET pair to be more easily compared across different optical configurations.
Different ways to transport ammonia in human and Mycobacterium tuberculosis NAD+ synthetases
Authors: Chuenchor Watchalee , Doukov Tzanko I. , Chang Kai-Ti , Resto Melissa , Yun Chang-Soo , Gerratana Barbara 
Published: January 2020

AbstractNAD+ synthetase is an essential enzyme of de novo and recycling pathways of NAD+ biosynthesis in Mycobacterium tuberculosis but not in humans. This bifunctional enzyme couples the NAD+ synthetase and glutaminase activities through an ammonia tunnel but free ammonia is also a substrate. Here we show that the Homo sapiens NAD+ synthetase (hsNadE) lacks substrate specificity for glutamine over ammonia and displays a modest activation of the glutaminase domain compared to tbNadE. We report the crystal structures of hsNadE and NAD+ synthetase from M. tuberculosis (tbNadE) with synthetase intermediate analogues. Based on the observed exclusive arrangements of the domains and of the intra- or inter-subunit tunnels we propose a model for the inter-domain communication mechanism for the regulation of glutamine-dependent activity and NH3 transport. The structural and mechanistic comparison herein reported between hsNadE and tbNadE provides also a starting point for future efforts in the development of anti-TB drugs.
Enabling remote quantum emission in 2D semiconductors via porous metallic networks
Authors: Fonseca Jose J. , Yeats Andrew L. , Blue Brandon , Zalalutdinov Maxim K. , Brintlinger Todd , Simpkins Blake S. , Ratchford Daniel C. , Culbertson James C. , Grim Joel Q. , Carter Samuel G. , Ishigami Masa , Stroud Rhonda M. , Cress Cory D. , Robinson Jeremy T. 
Published: January 2020

AbstractHere we report how two-dimensional crystal (2DC) overlayers influence the recrystallization of relatively thick metal films and the subsequent synergetic benefits this provides for coupling surface plasmon-polaritons (SPPs) to photon emission in 2D semiconductors. We show that annealing 2DC/Au films on SiO2 results in a reverse epitaxial process where initially nanocrystalline Au films gain texture, crystallographically orient with the 2D crystal overlayer, and form an oriented porous metallic network (OPEN) structure in which the 2DC can suspend above or coat the inside of the metal pores. Both laser excitation and exciton recombination in the 2DC semiconductor launch propagating SPPs in the OPEN film. Energy in-/out- coupling occurs at metal pore sites, alleviating the need for dielectric spacers between the metal and 2DC layer. At low temperatures, single-photon emitters (SPEs) are present across an OPEN-WSe2 film, and we demonstrate remote SPP-mediated excitation of SPEs at a distance of 17 μm.
Single-cell analysis based dissection of clonality in myelofibrosis
Authors: Mylonas Elena , Yoshida Kenichi , Frick Mareike , Hoyer Kaja , Christen Friederike , Kaeda Jaspal , Obenaus Matthias , Noerenberg Daniel , Hennch Cornelius , Chan Willy , Ochi Yotaro , Shiraishi Yuichi , Shiozawa Yusuke , Zenz Thorsten , Oakes Christopher C. , Sawitzki Birgit , Schwarz Michaela , Bullinger Lars , le Coutre Philipp , Rose-Zerilli Matthew J. J. , Ogawa Seishi , Damm Frederik 
Published: January 2020

AbstractCancer development is an evolutionary genomic process with parallels to Darwinian selection. It requires acquisition of multiple somatic mutations that collectively cause a malignant phenotype and continuous clonal evolution is often linked to tumor progression. Here, we show the clonal evolution structure in 15 myelofibrosis (MF) patients while receiving treatment with JAK inhibitors (mean follow-up 3.9 years). Whole-exome sequencing at multiple time points reveal acquisition of somatic mutations and copy number aberrations over time. While JAK inhibition therapy does not seem to create a clear evolutionary bottleneck, we observe a more complex clonal architecture over time, and appearance of unrelated clones. Disease progression associates with increased genetic heterogeneity and gain of RAS/RTK pathway mutations. Clonal diversity results in clone-specific expansion within different myeloid cell lineages. Single-cell genotyping of circulating CD34 + progenitor cells allows the reconstruction of MF phylogeny demonstrating loss of heterozygosity and parallel evolution as recurrent events.
Fungal community assembly in drought-stressed sorghum shows stochasticity, selection, and universal ecological dynamics
Authors: Gao Cheng , Montoya Liliam , Xu Ling , Madera Mary , Hollingsworth Joy , Purdom Elizabeth , Singan Vasanth , Vogel John , Hutmacher Robert B. , Dahlberg Jeffery A. , Coleman-Derr Devin , Lemaux Peggy G. , Taylor John W. 
Published: January 2020

AbstractCommunity assembly of crop-associated fungi is thought to be strongly influenced by deterministic selection exerted by the plant host, rather than stochastic processes. Here we use a simple, sorghum system with abundant sampling to show that stochastic forces (drift or stochastic dispersal) act on fungal community assembly in leaves and roots early in host development and when sorghum is drought stressed, conditions when mycobiomes are small. Unexpectedly, we find no signal for stochasticity when drought stress is relieved, likely due to renewed selection by the host. In our experimental system, the host compartment exerts the strongest effects on mycobiome assembly, followed by the timing of plant development and lastly by plant genotype. Using a dissimilarity-overlap approach, we find a universality in the forces of community assembly of the mycobiomes of the different sorghum compartments and in functional guilds of fungi.
Hand-foot-and-mouth disease virus receptor KREMEN1 binds the canyon of Coxsackie Virus A10
Authors: Zhao Yuguang , Zhou Daming , Ni Tao , Karia Dimple , Kotecha Abhay , Wang Xiangxi , Rao Zihe , Jones E. Yvonne , Fry Elizabeth E. , Ren Jingshan , Stuart David I. 
Published: January 2020

AbstractCoxsackievirus A10 (CV-A10) is responsible for an escalating number of severe infections in children, but no prophylactics or therapeutics are currently available. KREMEN1 (KRM1) is the entry receptor for the largest receptor-group of hand-foot-and-mouth disease causing viruses, which includes CV-A10. We report here structures of CV-A10 mature virus alone and in complex with KRM1 as well as of the CV-A10 A-particle. The receptor spans the viral canyon with a large footprint on the virus surface. The footprint has some overlap with that seen for the neonatal Fc receptor complexed with enterovirus E6 but is larger and distinct from that of another enterovirus receptor SCARB2. Reduced occupancy of a particle-stabilising pocket factor in the complexed virus and the presence of both unbound and expanded virus particles suggests receptor binding initiates a cascade of conformational changes that produces expanded particles primed for viral uncoating.
High-density information storage in an absolutely defined aperiodic sequence of monodisperse copolyester
Authors: Lee Jung Min , Koo Mo Beom , Lee Seul Woo , Lee Heelim , Kwon Junho , Shim Yul Hui , Kim So Youn , Kim Kyoung Taek 
Published: January 2020

AbstractSynthesis of a polymer composed of a large discrete number of chemically distinct monomers in an absolutely defined aperiodic sequence remains a challenge in polymer chemistry. The synthesis has largely been limited to oligomers having a limited number of repeating units due to the difficulties associated with the step-by-step addition of individual monomers to achieve high molecular weights. Here we report the copolymers of α-hydroxy acids, poly(phenyllactic-co-lactic acid) (PcL) built via the cross-convergent method from four dyads of monomers as constituent units. Our proposed method allows scalable synthesis of sequence-defined PcL in a minimal number of coupling steps from reagents in stoichiometric amounts. Digital information can be stored in an aperiodic sequence of PcL, which can be fully retrieved as binary code by mass spectrometry sequencing. The information storage density (bit/Da) of PcL is 50% higher than DNA, and the storage capacity of PcL can also be increased by adjusting the molecular weight (~38 kDa).
IBM Q Experience as a versatile experimental testbed for simulating open quantum systems
Authors: García-Pérez Guillermo , Rossi Matteo A. C. , Maniscalco Sabrina 
Published: January 2020

AbstractThe advent of noisy intermediate-scale quantum (NISQ) technology is changing rapidly the landscape and modality of research in quantum physics. NISQ devices, such as the IBM Q Experience, have very recently proven their capability as experimental platforms accessible to everyone around the globe. Until now, IBM Q Experience processors have mostly been used for quantum computation and simulation of closed systems. Here, we show that these devices are also able to implement a great variety of paradigmatic open quantum systems models, hence providing a robust and flexible testbed for open quantum systems theory. During the last decade an increasing number of experiments have successfully tackled the task of simulating open quantum systems in different platforms, from linear optics to trapped ions, from nuclear magnetic resonance (NMR) to cavity quantum electrodynamics. Generally, each individual experiment demonstrates a specific open quantum system model, or at most a specific class. Our main result is to prove the great versatility of the IBM Q Experience processors. Indeed, we experimentally implement one and two-qubit open quantum systems, both unital and non-unital dynamics, Markovian and non-Markovian evolutions. Moreover, we realise proof-of-principle reservoir engineering for entangled state generation, demonstrate collisional models, and verify revivals of quantum channel capacity and extractable work, caused by memory effects. All these results are obtained using IBM Q Experience processors publicly available and remotely accessible online.
The neurobiology of treatment-resistant schizophrenia: paths to antipsychotic resistance and a roadmap for future research
Authors: Potkin Steven G. , Kane John M. , Correll Christoph U. , Lindenmayer Jean-Pierre , Agid Ofer , Marder Stephen R. , Olfson Mark , Howes Oliver D. 
Published: January 2020

AbstractTreatment-resistant schizophrenia (TRS), the persistence of positive symptoms despite ≥2 trials of adequate dose and duration of antipsychotic medication with documented adherence, is a serious clinical problem with heterogeneous presentations. TRS can vary in its onset (at the first episode of psychosis or upon relapse), in its severity, and in the response to subsequent therapeutic interventions (i.e., clozapine, electroconvulsive therapy). The heterogeneity of TRS indicates that the underlying neurobiology of TRS may differ not only from treatment-responsive schizophrenia but also among patients with TRS. Several hypotheses have been proposed for the neurobiological mechanisms underlying TRS, including dopamine supersensitivity, hyperdopaminergic and normodopaminergic subtypes, glutamate dysregulation, inflammation and oxidative stress, and serotonin dysregulation. Research supporting these hypotheses is limited in part by variations in the criteria used to define TRS, as well as by the biological and clinical heterogeneity of TRS. Clinical trial designs for new treatments should be informed by this heterogeneity, and further clinical research is needed to more clearly understand the underlying neurobiology of TRS and to optimize treatment for patients with TRS.