bluuebunny/crossref_metadata_2025_split huggingface dataset:
CMTM6 expressed on the adaxonal Schwann cell surface restricts axonal diameters in peripheral nerves
Authors: Eichel Maria A. , Gargareta Vasiliki-Ilya , D’Este Elisa , Fledrich Robert , Kungl Theresa , Buscham Tobias J. , Lüders Katja A. , Miracle Cristina , Jung Ramona B. , Distler Ute , Kusch Kathrin , Möbius Wiebke , Hülsmann Swen , Tenzer Stefan , Nave Klaus-Armin , Werner Hauke B. 
Published: September 2020

AbstractThe velocity of nerve conduction is moderately enhanced by larger axonal diameters and potently sped up by myelination of axons. Myelination thus allows rapid impulse propagation with reduced axonal diameters; however, no myelin-dependent mechanism has been reported that restricts radial growth of axons. By label-free proteomics, STED-microscopy and cryo-immuno electron-microscopy we here identify CMTM6 (chemokine-like factor-like MARVEL-transmembrane domain-containing family member-6) as a myelin protein specifically localized to the Schwann cell membrane exposed to the axon. We find that disruption of Cmtm6-expression in Schwann cells causes a substantial increase of axonal diameters but does not impair myelin biogenesis, radial sorting or integrity of axons. Increased axonal diameters correlate with accelerated sensory nerve conduction and sensory responses and perturbed motor performance. These data show that Schwann cells utilize CMTM6 to restrict the radial growth of axons, which optimizes nerve function.
Single-cell transcriptomes of pancreatic preinvasive lesions and cancer reveal acinar metaplastic cells’ heterogeneity
Authors: Schlesinger Yehuda , Yosefov-Levi Oshri , Kolodkin-Gal Dror , Granit Roy Zvi , Peters Luriano , Kalifa Rachel , Xia Lei , Nasereddin Abdelmajeed , Shiff Idit , Amran Osher , Nevo Yuval , Elgavish Sharona , Atlan Karine , Zamir Gideon , Parnas Oren 
Published: September 2020

AbstractAcinar metaplasia is an initial step in a series of events that can lead to pancreatic cancer. Here we perform single-cell RNA-sequencing of mouse pancreas during the progression from preinvasive stages to tumor formation. Using a reporter gene, we identify metaplastic cells that originated from acinar cells and express two transcription factors, Onecut2 and Foxq1. Further analyses of metaplastic acinar cell heterogeneity define six acinar metaplastic cell types and states, including stomach-specific cell types. Localization of metaplastic cell types and mixture of different metaplastic cell types in the same pre-malignant lesion is shown. Finally, single-cell transcriptome analyses of tumor-associated stromal, immune, endothelial and fibroblast cells identify signals that may support tumor development, as well as the recruitment and education of immune cells. Our findings are consistent with the early, premalignant formation of an immunosuppressive environment mediated by interactions between acinar metaplastic cells and other cells in the microenvironment.
A gas-to-particle conversion mechanism helps to explain atmospheric particle formation through clustering of iodine oxides
Authors: Gómez Martín Juan Carlos , Lewis Thomas R. , Blitz Mark A. , Plane John M. C. , Kumar Manoj , Francisco Joseph S. , Saiz-Lopez Alfonso 
Published: September 2020

AbstractEmitted from the oceans, iodine-bearing molecules are ubiquitous in the atmosphere and a source of new atmospheric aerosol particles of potentially global significance. However, its inclusion in atmospheric models is hindered by a lack of understanding of the first steps of the photochemical gas-to-particle conversion mechanism. Our laboratory results show that under a high humidity and low HOx regime, the recently proposed nucleating molecule (iodic acid, HOIO2) does not form rapidly enough, and gas-to-particle conversion proceeds by clustering of iodine oxides (IxOy), albeit at slower rates than under dryer conditions. Moreover, we show experimentally that gas-phase HOIO2 is not necessary for the formation of HOIO2-containing particles. These insights help to explain new particle formation in the relatively dry polar regions and, more generally, provide for the first time a thermochemically feasible molecular mechanism from ocean iodine emissions to atmospheric particles that is currently missing in model calculations of aerosol radiative forcing.
DNA methylation study of Huntington’s disease and motor progression in patients and in animal models
Authors: Lu Ake T. , Narayan Pritika , Grant Matthew J. , Langfelder Peter , Wang Nan , Kwak Seung , Wilkinson Hilary , Chen Richard Z. , Chen Jian , Simon Bawden C. , Rudiger Skye R. , Ciosi Marc , Chatzi Afroditi , Maxwell Alastair , Hore Timothy A. , Aaronson Jeff , Rosinski Jim , Preiss Alicia , Vogt Thomas F. , Coppola Giovanni , Monckton Darren , Snell Russell G. , William Yang X. , Horvath Steve 
Published: September 2020

AbstractAlthough Huntington’s disease (HD) is a well studied Mendelian genetic disorder, less is known about its associated epigenetic changes. Here, we characterize DNA methylation levels in six different tissues from 3 species: a mouse huntingtin (Htt) gene knock-in model, a transgenic HTT sheep model, and humans. Our epigenome-wide association study (EWAS) of human blood reveals that HD mutation status is significantly (p < 10−7) associated with 33 CpG sites, including the HTT gene (p = 6.5 × 10−26). These Htt/HTT associations were replicated in the Q175 Htt knock-in mouse model (p = 6.0 × 10−8) and in the transgenic sheep model (p = 2.4 × 10−88). We define a measure of HD motor score progression among manifest HD cases based on multiple clinical assessments. EWAS of motor progression in manifest HD cases exhibits significant (p < 10−7) associations with methylation levels at three loci: near PEX14 (p = 9.3 × 10−9), GRIK4 (p = 3.0 × 10−8), and COX4I2 (p = 6.5 × 10−8). We conclude that HD is accompanied by profound changes of DNA methylation levels in three mammalian species.
Exhausted CD8+ T cells exhibit low and strongly inhibited TCR signaling during chronic LCMV infection
Authors: Sandu Ioana , Cerletti Dario , Claassen Manfred , Oxenius Annette 
Published: September 2020

AbstractChronic viral infections are often associated with impaired CD8+ T cell function, referred to as exhaustion. Although the molecular and cellular circuits involved in CD8+ T cell exhaustion are well defined, with sustained presence of antigen being one important parameter, how much T cell receptor (TCR) signaling is actually ongoing in vivo during established chronic infection is unclear. Here, we characterize the in vivo TCR signaling of virus-specific exhausted CD8+ T cells in a mouse model, leveraging TCR signaling reporter mice in combination with transcriptomics. In vivo signaling in exhausted cells is low, in contrast to their in vitro signaling potential, and despite antigen being abundantly present. Both checkpoint blockade and adoptive transfer of naïve target cells increase TCR signaling, demonstrating that engagement of co-inhibitory receptors curtails CD8+ T cell signaling and function in vivo.
Mantle flow distribution beneath the California margin
Authors: Barbot Sylvain 
Published: September 2020

AbstractAlthough the surface deformation of tectonic plate boundaries is well determined by geological and geodetic measurements, the pattern of flow below the lithosphere remains poorly constrained. We use the crustal velocity field of the Plate Boundary Observatory to illuminate the distribution of horizontal flow beneath the California margin. At lower-crustal and upper-mantle depths, the boundary between the Pacific and North American plates is off-centered from the San Andreas fault, concentrated in a region that encompasses the trace of nearby active faults. A major step is associated with return flow below the Eastern California Shear Zone, leading to the extrusion of the Mojave block and a re-distribution of fault activity since the Pleistocene. Major earthquakes in California have occurred above the regions of current plastic strain accumulation. Deformation is mechanically coupled from the crust to the asthenosphere, with mantle flow overlaid by a kinematically consistent network of faults in the brittle crust.
Functional regulation of an ancestral RAG transposon ProtoRAG by a trans-acting factor YY1 in lancelet
Authors: Liu Song , Yuan Shaochun , Gao Xiaoman , Tao Xin , Yu Wenjuan , Li Xu , Chen Shangwu , Xu Anlong 
Published: September 2020

AbstractThe discovery of ancestral RAG transposons in early deuterostomia reveals the origin of vertebrate V(D)J recombination. Here, we analyze the functional regulation of a RAG transposon, ProtoRAG, in lancelet. We find that a specific interaction between the cis-acting element within the TIR sequences of ProtoRAG and a trans-acting factor, lancelet YY1-like (bbYY1), is important for the transcriptional regulation of lancelet RAG-like genes (bbRAG1L and bbRAG2L). Mechanistically, bbYY1 suppresses the transposition of ProtoRAG; meanwhile, bbYY1 promotes host DNA rejoins (HDJ) and TIR-TIR joints (TTJ) after TIR-dependent excision by facilitating the binding of bbRAG1L/2 L to TIR-containing DNA, and by interacting with the bbRAG1L/2 L complex. Our data thus suggest that bbYY1 has dual functions in fine-tuning the activity of ProtoRAG and maintaining the genome stability of the host.
Graphdiyne-modified TiO2 nanofibers with osteoinductive and enhanced photocatalytic antibacterial activities to prevent implant infection
Authors: Wang Rui , Shi Miusi , Xu Feiyan , Qiu Yun , Zhang Peng , Shen Kailun , Zhao Qin , Yu Jiaguo , Zhang Yufeng 
Published: September 2020

AbstractTitanium implants have been widely used in bone tissue engineering for decades. However, orthopedic implant-associated infections increase the risk of implant failure and even lead to amputation in severe cases. Although TiO2has photocatalytic activity to produce reactive oxygen species (ROS), the recombination of generated electrons and holes limits its antibacterial ability. Here, we describe a graphdiyne (GDY) composite TiO2nanofiber that combats implant infections through enhanced photocatalysis and prolonged antibacterial ability. In addition, GDY-modified TiO2nanofibers exert superior biocompatibility and osteoinductive abilities for cell adhesion and differentiation, thus contributing to the bone tissue regeneration process in drug-resistant bacteria-induced implant infection.
Converting microwave and telecom photons with a silicon photonic nanomechanical interface
Authors: Arnold G. , Wulf M. , Barzanjeh S. , Redchenko E. S. , Rueda A. , Hease W. J. , Hassani F. , Fink J. M. 
Published: September 2020

AbstractPractical quantum networks require low-loss and noise-resilient optical interconnects as well as non-Gaussian resources for entanglement distillation and distributed quantum computation. The latter could be provided by superconducting circuits but existing solutions to interface the microwave and optical domains lack either scalability or efficiency, and in most cases the conversion noise is not known. In this work we utilize the unique opportunities of silicon photonics, cavity optomechanics and superconducting circuits to demonstrate a fully integrated, coherent transducer interfacing the microwave X and the telecom S bands with a total (internal) bidirectional transduction efficiency of 1.2% (135%) at millikelvin temperatures. The coupling relies solely on the radiation pressure interaction mediated by the femtometer-scale motion of two silicon nanobeams reaching a Vπ as low as 16 μV for sub-nanowatt pump powers. Without the associated optomechanical gain, we achieve a total (internal) pure conversion efficiency of up to 0.019% (1.6%), relevant for future noise-free operation on this qubit-compatible platform.
Substantial underestimation of SARS-CoV-2 infection in the United States
Authors: Wu Sean L. , Mertens Andrew N. , Crider Yoshika S. , Nguyen Anna , Pokpongkiat Nolan N. , Djajadi Stephanie , Seth Anmol , Hsiang Michelle S. , Colford John M. , Reingold Art , Arnold Benjamin F. , Hubbard Alan , Benjamin-Chung Jade 
Published: September 2020

AbstractAccurate estimates of the burden of SARS-CoV-2 infection are critical to informing pandemic response. Confirmed COVID-19 case counts in the U.S. do not capture the total burden of the pandemic because testing has been primarily restricted to individuals with moderate to severe symptoms due to limited test availability. Here, we use a semi-Bayesian probabilistic bias analysis to account for incomplete testing and imperfect diagnostic accuracy. We estimate 6,454,951 cumulative infections compared to 721,245 confirmed cases (1.9% vs. 0.2% of the population) in the United States as of April 18, 2020. Accounting for uncertainty, the number of infections during this period was 3 to 20 times higher than the number of confirmed cases. 86% (simulation interval: 64–99%) of this difference is due to incomplete testing, while 14% (0.3–36%) is due to imperfect test accuracy. The approach can readily be applied in future studies in other locations or at finer spatial scale to correct for biased testing and imperfect diagnostic accuracy to provide a more realistic assessment of COVID-19 burden.
Photo-mediated selective deconstructive geminal dihalogenation of trisubstituted alkenes
Authors: Wang Han , Toh Ren Wei , Shi Xiangcheng , Wang Tonglin , Cong Xu , Wu Jie 
Published: September 2020

AbstractSelective deconstructive functionalization of alkenes, other than the well-established olefin metathesis and ozonolysis, to produce densely functionalized molecular scaffolds is highly attractive but challenging. Here we report an efficient photo-mediated deconstructive germinal dihalogenation of carbon-carbon double bonds. A wide range of geminal diiodoalkanes and bromo(iodo)alkanes (>40 examples) are directly prepared from various trisubstituted alkenes, including both cyclic and acyclic olefins. This C=C cleavage is highly chemoselective and produces geminal dihalide ketones in good yields. Mechanistic investigations suggest a formation of alkyl hypoiodites from benzyl alcohols and N-iodoimides, which undergo light-induced homolytic cleavage to generate active oxygen radical species.
A distinct lineage of Caudovirales that encodes a deeply branching multi-subunit RNA polymerase
Authors: Weinheimer Alaina R. , Aylward Frank O. 
Published: September 2020

AbstractBacteriophages play critical roles in the biosphere, but their vast genomic diversity has obscured their evolutionary origins, and phylogenetic analyses have traditionally been hindered by their lack of universal phylogenetic marker genes. In this study we mine metagenomic data and identify a clade of Caudovirales that encodes the β and β′ subunits of multi-subunit RNA polymerase (RNAP), a high-resolution phylogenetic marker which enables detailed evolutionary analyses. Our RNAP phylogeny revealed that the Caudovirales RNAP forms a clade distinct from cellular homologs, suggesting an ancient acquisition of this enzyme. Within these multimeric RNAP-encoding Caudovirales (mReC), we find that the similarity of major capsid proteins and terminase large subunits further suggests they form a distinct clade with common evolutionary origin. Our study characterizes a clade of RNAP-encoding Caudovirales and suggests the ancient origin of this enzyme in this group, underscoring the important role of viruses in the early evolution of life on Earth.
Real-time monitoring of single ZTP riboswitches reveals a complex and kinetically controlled decision landscape
Authors: Hua Boyang , Jones Christopher P. , Mitra Jaba , Murray Peter J. , Rosenthal Rebecca , Ferré-D’Amaré Adrian R. , Ha Taekjip 
Published: September 2020

AbstractRNAs begin to fold and function during transcription. Riboswitches undergo cotranscriptional switching in the context of transcription elongation, RNA folding, and ligand binding. To investigate how these processes jointly modulate the function of the folate stress-sensing Fusobacterium ulcerans ZTP riboswitch, we apply a single-molecule vectorial folding (VF) assay in which an engineered superhelicase Rep-X sequentially releases fluorescently labeled riboswitch RNA from a heteroduplex in a 5′-to-3′ direction, at ~60 nt s−1 [comparable to the speed of bacterial RNA polymerase (RNAP)]. We demonstrate that the ZTP riboswitch is kinetically controlled and that its activation is favored by slower unwinding, strategic pausing between but not before key folding elements, or a weakened transcription terminator. Real-time single-molecule monitoring captures folding riboswitches in multiple states, including an intermediate responsible for delayed terminator formation. These results show how individual nascent RNAs occupy distinct channels within the folding landscape that controls the fate of the riboswitch.
Re-imagining fMRI for awake behaving infants
Authors: Ellis C. T. , Skalaban L. J. , Yates T. S. , Bejjanki V. R. , Córdova N. I. , Turk-Browne N. B. 
Published: September 2020

AbstractThousands of functional magnetic resonance imaging (fMRI) studies have provided important insight into the human brain. However, only a handful of these studies tested infants while they were awake, because of the significant and unique methodological challenges involved. We report our efforts to address these challenges, with the goal of creating methods for awake infant fMRI that can reveal the inner workings of the developing, preverbal mind. We use these methods to collect and analyze two fMRI datasets obtained from infants during cognitive tasks, released publicly with this paper. In these datasets, we explore and evaluate data quantity and quality, task-evoked activity, and preprocessing decisions. We disseminate these methods by sharing two software packages that integrate infant-friendly cognitive tasks and eye-gaze monitoring with fMRI acquisition and analysis. These resources make fMRI a feasible and accessible technique for cognitive neuroscience in awake and behaving human infants.
Transgenerational inheritance of impaired larval T cell development in zebrafish
Authors: Iwanami Norimasa , Lawir Divine-Fondzenyuy , Sikora Katarzyna , O´Meara Connor , Takeshita Kohei , Schorpp Michael , Boehm Thomas 
Published: September 2020

AbstractEvidence for transgenerational inheritance of epigenetic information in vertebrates is scarce. Aberrant patterns of DNA methylation in gametes may set the stage for transmission into future generations. Here, we describe a viable hypomorphic allele of dnmt1 in zebrafish that causes widespread demethylation of CpG dinucleotides in sperm and somatic tissues. We find that homozygous mutants are essentially normal, with the exception of drastically impaired lymphopoiesis, affecting both larval and adult phases of T cell development. The phenotype of impaired larval (but not adult) T cell development is transmitted to subsequent generations by genotypically wildtype fish. We further find that about 200 differentially methylated regions in sperm DNA of transmitting and non-transmitting males, including hypermethylated sites associated with runx3 and rptor genes, whose reduced activities are associated with impaired larval T cell development. Our results indicate a particular sensitivity of larval T cell development to transgenerationally inherited epimutations.
Wrapping glia regulates neuronal signaling speed and precision in the peripheral nervous system of Drosophila
Authors: Kottmeier Rita , Bittern Jonas , Schoofs Andreas , Scheiwe Frederieke , Matzat Till , Pankratz Michael , Klämbt Christian 
Published: September 2020

AbstractThe functionality of the nervous system requires transmission of information along axons with high speed and precision. Conductance velocity depends on axonal diameter whereas signaling precision requires a block of electrical crosstalk between axons, known as ephaptic coupling. Here, we use the peripheral nervous system of Drosophila larvae to determine how glia regulates axonal properties. We show that wrapping glial differentiation depends on gap junctions and FGF-signaling. Abnormal glial differentiation affects axonal diameter and conductance velocity and causes mild behavioral phenotypes that can be rescued by a sphingosine-rich diet. Ablation of wrapping glia does not further impair axonal diameter and conductance velocity but causes a prominent locomotion phenotype that cannot be rescued by sphingosine. Moreover, optogenetically evoked locomotor patterns do not depend on conductance speed but require the presence of wrapping glial processes. In conclusion, our data indicate that wrapping glia modulates both speed and precision of neuronal signaling.
Swelling-strengthening hydrogels by embedding with deformable nanobarriers
Authors: Wu Feng , Pang Yan , Liu Jinyao 
Published: September 2020

AbstractBiological tissues, such as muscle, can increase their mechanical strength after swelling due to the existence of many biological membrane barriers that can regulate the transmembrane transport of water molecules and ions. Oppositely, typical synthetic materials show a swelling-weakening behavior, which always suffers from a sharp decline in mechanical strength after swelling, because of the dilution of the network. Here, we describe a swelling-strengthening phenomenon of polymer materials achieved by a bioinspired strategy. Liposomal membrane nanobarriers are covalently embedded in a crosslinked network to regulate transmembrane transport. After swelling, the stretched network deforms the liposomes and subsequently initiates the transmembrane diffusion of the encapsulated molecules that can trigger the formation of a new network from the preloaded precursor. Thanks to the tough nature of the double-network structure, the swelling-strengthening phenomenon is achieved to polymer hydrogels successfully. Swelling-triggered self-strengthening enables the development of various dynamic materials.
Scaling behavior of the quantum phase transition from a quantum-anomalous-Hall insulator to an axion insulator
Authors: Wu Xinyu , Xiao Di , Chen Chui-Zhen , Sun Jian , Zhang Ling , Chan Moses H. W. , Samarth Nitin , Xie X. C. , Lin Xi , Chang Cui-Zu 
Published: September 2020

AbstractThe phase transitions from one plateau to the next plateau or to an insulator in quantum Hall and quantum anomalous Hall (QAH) systems have revealed universal scaling behaviors. A magnetic-field-driven quantum phase transition from a QAH insulator to an axion insulator was recently demonstrated in magnetic topological insulator sandwich samples. Here, we show that the temperature dependence of the derivative of the longitudinal resistance on magnetic field at the transition point follows a characteristic power-law that indicates a universal scaling behavior for the QAH to axion insulator phase transition. Similar to the quantum Hall plateau to plateau transition, the QAH to axion insulator transition can also be understood by the Chalker–Coddington network model. We extract a critical exponent κ ~ 0.38 ± 0.02 in agreement with recent high-precision numerical results on the correlation length exponent of the Chalker–Coddington model at ν ~ 2.6, rather than the generally-accepted value of 2.33.