bluuebunny/crossref_metadata_2025_split huggingface dataset:
TARM1 contributes to development of arthritis by activating dendritic cells through recognition of collagens
Authors: Yabe Rikio , Chung Soo-Hyun , Murayama Masanori A. , Kubo Sachiko , Shimizu Kenji , Akahori Yukiko , Maruhashi Takumi , Seno Akimasa , Kaifu Tomonori , Saijo Shinobu , Iwakura Yoichiro 
Published: January 2021

AbstractTARM1 is a member of the leukocyte immunoglobulin-like receptor family and stimulates macrophages and neutrophils in vitro by associating with FcRγ. However, the function of this molecule in the regulation of the immune system is unclear. Here, we show thatTarm1expression is elevated in the joints of rheumatoid arthritis mouse models, and the development of collagen-induced arthritis (CIA) is suppressed inTarm1–/–mice. T cell priming against type 2 collagen is suppressed inTarm1–/–mice and antigen-presenting ability of GM-CSF-induced dendritic cells (GM-DCs) fromTarm1–/–mouse bone marrow cells is impaired. We show that type 2 collagen is a functional ligand for TARM1 on GM-DCs and promotes DC maturation. Furthermore, soluble TARM1-Fc and TARM1-Flag inhibit DC maturation and administration of TARM1-Fc blocks the progression of CIA in mice. These results indicate that TARM1 is an important stimulating factor of dendritic cell maturation and could be a good target for the treatment of autoimmune diseases.
Non-invasive assessment of telomere maintenance mechanisms in brain tumors
Authors: Viswanath Pavithra , Batsios Georgios , Mukherjee Joydeep , Gillespie Anne Marie , Larson Peder E. Z. , Luchman H. Artee , Phillips Joanna J. , Costello Joseph F. , Pieper Russell O. , Ronen Sabrina M. 
Published: January 2021

AbstractTelomere maintenance is a universal hallmark of cancer. Most tumors including low-grade oligodendrogliomas use telomerase reverse transcriptase (TERT) expression for telomere maintenance while astrocytomas use the alternative lengthening of telomeres (ALT) pathway. Although TERT and ALT are hallmarks of tumor proliferation and attractive therapeutic targets, translational methods of imaging TERT and ALT are lacking. Here we show that TERT and ALT are associated with unique 1H-magnetic resonance spectroscopy (MRS)-detectable metabolic signatures in genetically-engineered and patient-derived glioma models and patient biopsies. Importantly, we have leveraged this information to mechanistically validate hyperpolarized [1-13C]-alanine flux to pyruvate as an imaging biomarker of ALT status and hyperpolarized [1-13C]-alanine flux to lactate as an imaging biomarker of TERT status in low-grade gliomas. Collectively, we have identified metabolic biomarkers of TERT and ALT status that provide a way of integrating critical oncogenic information into non-invasive imaging modalities that can improve tumor diagnosis and treatment response monitoring.
Anomalous collapses of Nares Strait ice arches leads to enhanced export of Arctic sea ice
Authors: Moore G. W. K. , Howell S. E. L. , Brady M. , Xu X. , McNeil K. 
Published: January 2021

AbstractThe ice arches that usually develop at the northern and southern ends of Nares Strait play an important role in modulating the export of Arctic Ocean multi-year sea ice. The Arctic Ocean is evolving towards an ice pack that is younger, thinner, and more mobile and the fate of its multi-year ice is becoming of increasing interest. Here, we use sea ice motion retrievals from Sentinel-1 imagery to report on the recent behavior of these ice arches and the associated ice fluxes. We show that the duration of arch formation has decreased over the past 20 years, while the ice area and volume fluxes along Nares Strait have both increased. These results suggest that a transition is underway towards a state where the formation of these arches will become atypical with a concomitant increase in the export of multi-year ice accelerating the transition towards a younger and thinner Arctic ice pack.
Filamentous recombinant human Tau activates primary astrocytes via an integrin receptor complex
Authors: Wang Peng , Ye Yihong 
Published: January 2021

AbstractMicrotubule-associated protein Tau can form protein aggregates transmissible within the brain, correlating with the progression of tauopathies in humans. The transmission of aggregates requires neuron-released Tau to interact with surface receptors on target cells. However, the underlying molecular mechanisms in astrocytes and downstream effects are unclear. Here, using a spatially resolved proteomic mapping strategy, we show that integrin αV/β1 receptor binds recombinant human Tau, mediating the entry of Tau fibrils in astrocytes. The binding of distinct Tau species to the astrocytic αV/β1 receptor differentially activate integrin signaling. Furthermore, Tau-mediated activation of integrin signaling results in NFκB activation, causing upregulation of pro-inflammatory cytokines and chemokines, induction of a sub-group of neurotoxic astrocytic markers, and release of neurotoxic factors. Our findings suggest that filamentous recombinant human Tau-mediated activation of integrin signaling induces astrocyte conversion towards a neurotoxic state, providing a mechanistic insight into tauopathies.
The aging transcriptome and cellular landscape of the human lung in relation to SARS-CoV-2
Authors: Chow Ryan D. , Majety Medha , Chen Sidi 
Published: January 2021

AbstractAge is a major risk factor for severe coronavirus disease-2019 (COVID-19). Here, we interrogate the transcriptional features and cellular landscape of the aging human lung. By intersecting these age-associated changes with experimental data on SARS-CoV-2, we identify several factors that may contribute to the heightened severity of COVID-19 in older populations. The aging lung is transcriptionally characterized by increased cell adhesion and stress responses, with reduced mitochondria and cellular replication. Deconvolution analysis reveals that the proportions of alveolar type 2 cells, proliferating basal cells, goblet cells, and proliferating natural killer/T cells decrease with age, whereas alveolar fibroblasts, pericytes, airway smooth muscle cells, endothelial cells and IGSF21+ dendritic cells increase with age. Several age-associated genes directly interact with the SARS-CoV-2 proteome. Age-associated genes are also dysregulated by SARS-CoV-2 infection in vitro and in patients with severe COVID-19. These analyses illuminate avenues for further studies on the relationship between age and COVID-19.
QKI is a critical pre-mRNA alternative splicing regulator of cardiac myofibrillogenesis and contractile function
Authors: Chen Xinyun , Liu Ying , Xu Chen , Ba Lina , Liu Zhuo , Li Xiuya , Huang Jie , Simpson Ed , Gao Hongyu , Cao Dayan , Sheng Wei , Qi Hanping , Ji Hongrui , Sanderson Maria , Cai Chen-Leng , Li Xiaohui , Yang Lei , Na Jie , Yamamura Kenichi , Liu Yunlong , Huang Guoying , Shou Weinian , Sun Ning 
Published: January 2021

AbstractThe RNA-binding protein QKI belongs to the hnRNP K-homology domain protein family, a well-known regulator of pre-mRNA alternative splicing and is associated with several neurodevelopmental disorders.Qkiis found highly expressed in developing and adult hearts. By employing the human embryonic stem cell (hESC) to cardiomyocyte differentiation system and generating QKI-deficient hESCs (hESCs-QKIdel) using CRISPR/Cas9 gene editing technology, we analyze the physiological role of QKI in cardiomyocyte differentiation, maturation, and contractile function. hESCs-QKIdellargely maintain normal pluripotency and normal differentiation potential for the generation of early cardiogenic progenitors, but they fail to transition into functional cardiomyocytes. In this work, by using a series of transcriptomic, cell and biochemical analyses, and the Qki-deficient mouse model, we demonstrate that QKI is indispensable to cardiac sarcomerogenesis and cardiac function through its regulation of alternative splicing in genes involved in Z-disc formation and contractile physiology, suggesting thatQKIis associated with the pathogenesis of certain forms of cardiomyopathies.
Minutes-timescale 3D isotropic imaging of entire organs at subcellular resolution by content-aware compressed-sensing light-sheet microscopy
Authors: Fang Chunyu , Yu Tingting , Chu Tingting , Feng Wenyang , Zhao Fang , Wang Xuechun , Huang Yujie , Li Yusha , Wan Peng , Mei Wei , Zhu Dan , Fei Peng 
Published: January 2021

AbstractRapid 3D imaging of entire organs and organisms at cellular resolution is a recurring challenge in life science. Here we report on a computational light-sheet microscopy able to achieve minute-timescale high-resolution mapping of entire macro-scale organs. Through combining a dual-side confocally-scanned Bessel light-sheet illumination which provides thinner-and-wider optical sectioning of deep tissues, with a content-aware compressed sensing (CACS) computation pipeline which further improves the contrast and resolution based on a single acquisition, our approach yields 3D images with high, isotropic spatial resolution and rapid acquisition over two-order-of-magnitude faster than conventional 3D microscopy implementations. We demonstrate the imaging of whole brain (~400 mm3), entire gastrocnemius and tibialis muscles (~200 mm3) of mouse at ultra-high throughput of 5~10 min per sample and post-improved subcellular resolution of ~ 1.5 μm (0.5-μm iso-voxel size). Various system-level cellular analyses, such as mapping cell populations at different brain sub-regions, tracing long-distance projection neurons over the entire brain, and calculating neuromuscular junction occupancy across whole muscle, are also readily accomplished by our method.
The patterns of deleterious mutations during the domestication of soybean
Authors: Kim Myung-Shin , Lozano Roberto , Kim Ji Hong , Bae Dong Nyuk , Kim Sang-Tae , Park Jung-Ho , Choi Man Soo , Kim Jaehyun , Ok Hyun-Choong , Park Soo-Kwon , Gore Michael A. , Moon Jung-Kyung , Jeong Soon-Chun 
Published: January 2021

AbstractGlobally, soybean is a major protein and oil crop. Enhancing our understanding of the soybean domestication and improvement process helps boost genomics-assisted breeding efforts. Here we present a genome-wide variation map of 10.6 million single-nucleotide polymorphisms and 1.4 million indels for 781 soybean individuals which includes 418 domesticated (Glycine max), 345 wild (Glycine soja), and 18 natural hybrid (G. max/G. soja) accessions. We describe the enhanced detection of 183 domestication-selective sweeps and the patterns of putative deleterious mutations during domestication and improvement. This predominantly selfing species shows 7.1% reduction of overall deleterious mutations in domesticated soybean relative to wild soybean and a further 1.4% reduction from landrace to improved accessions. The detected domestication-selective sweeps also show reduced levels of deleterious alleles. Importantly, genotype imputation with this resource increases the mapping resolution of genome-wide association studies for seed protein and oil traits in a soybean diversity panel.
Error correction enables use of Oxford Nanopore technology for reference-free transcriptome analysis
Authors: Sahlin Kristoffer , Medvedev Paul 
Published: January 2021

AbstractOxford Nanopore (ONT) is a leading long-read technology which has been revolutionizing transcriptome analysis through its capacity to sequence the majority of transcripts from end-to-end. This has greatly increased our ability to study the diversity of transcription mechanisms such as transcription initiation, termination, and alternative splicing. However, ONT still suffers from high error rates which have thus far limited its scope to reference-based analyses. When a reference is not available or is not a viable option due to reference-bias, error correction is a crucial step towards the reconstruction of the sequenced transcripts and downstream sequence analysis of transcripts. In this paper, we present a novel computational method to error correct ONT cDNA sequencing data, called isONcorrect. IsONcorrect is able to jointly use all isoforms from a gene during error correction, thereby allowing it to correct reads at low sequencing depths. We are able to obtain a median accuracy of 98.9–99.6%, demonstrating the feasibility of applying cost-effective cDNA full transcript length sequencing for reference-free transcriptome analysis.
Self-strengthening biphasic nanoparticle assemblies with intrinsic catch bonds
Authors: Dansuk Kerim C. , Keten Sinan 
Published: January 2021

AbstractProtein–ligand complexes with catch bonds exhibit prolonged lifetimes when subject to tensile force, which is a desirable yet elusive attribute for man-made nanoparticle interfaces and assemblies. Most designs proposed so far rely on macromolecular linkers with complicated folds rather than particles exhibiting simple dynamic shapes. Here, we establish a scissor-type X-shaped particle design for achieving intrinsic catch bonding ability with tunable force-enhanced lifetimes under thermal excitations. Molecular dynamics simulations are carried out to illustrate equilibrium self-assembly and force-enhanced bond lifetime of dimers and fibers facilitated by secondary interactions that form under tensile force. The non-monotonic force dependence of the fiber breaking kinetics is well-estimated by an analytical model. Our design concepts for shape-changing particles illuminates a path towards novel nanoparticle or colloidal assemblies that have the passive ability to tune the strength of their interfaces with applied force, setting the stage for self-assembling materials with novel mechanical functions and rheological properties.
Long first exons and epigenetic marks distinguish conserved pachytene piRNA clusters from other mammalian genes
Authors: Yu Tianxiong , Fan Kaili , Özata Deniz M. , Zhang Gen , Fu Yu , Theurkauf William E. , Zamore Phillip D. , Weng Zhiping 
Published: January 2021

AbstractIn the male germ cells of placental mammals, 26–30-nt-long PIWI-interacting RNAs (piRNAs) emerge when spermatocytes enter the pachytene phase of meiosis. In mice, pachytene piRNAs derive from ~100 discrete autosomal loci that produce canonical RNA polymerase II transcripts. These piRNA clusters bear 5′ caps and 3′ poly(A) tails, and often contain introns that are removed before nuclear export and processing into piRNAs. What marks pachytene piRNA clusters to produce piRNAs, and what confines their expression to the germline? We report that an unusually long first exon (≥ 10 kb) or a long, unspliced transcript correlates with germline-specific transcription and piRNA production. Our integrative analysis of transcriptome, piRNA, and epigenome datasets across multiple species reveals that a long first exon is an evolutionarily conserved feature of pachytene piRNA clusters. Furthermore, a highly methylated promoter, often containing a low or intermediate level of CG dinucleotides, correlates with germline expression and somatic silencing of pachytene piRNA clusters. Pachytene piRNA precursor transcripts bind THOC1 and THOC2, THO complex subunits known to promote transcriptional elongation and mRNA nuclear export. Together, these features may explain why the major sources of pachytene piRNA clusters specifically generate these unique small RNAs in the male germline of placental mammals.
Metaxins are core components of mitochondrial transport adaptor complexes
Authors: Zhao Yinsuo , Song Eli , Wang Wenjuan , Hsieh Chung-Han , Wang Xinnan , Feng Wei , Wang Xiangming , Shen Kang 
Published: January 2021

AbstractTrafficking of mitochondria into dendrites and axons plays an important role in the physiology and pathophysiology of neurons. Mitochondrial outer membrane protein Miro and adaptor proteins TRAKs/Milton link mitochondria to molecular motors. Here we show that metaxins MTX-1 and MTX-2 contribute to mitochondrial transport into both dendrites and axons of C. elegans neurons. MTX1/2 bind to MIRO-1 and kinesin light chain KLC-1, forming a complex to mediate kinesin-1-based movement of mitochondria, in which MTX-1/2 are essential and MIRO-1 plays an accessory role. We find that MTX-2, MIRO-1, and TRAK-1 form another distinct adaptor complex to mediate dynein-based transport. Additionally, we show that failure of mitochondrial trafficking in dendrites causes age-dependent dendrite degeneration. We propose that MTX-2 and MIRO-1 form the adaptor core for both motors, while MTX-1 and TRAK-1 specify each complex for kinesin-1 and dynein, respectively. MTX-1 and MTX-2 are also required for mitochondrial transport in human neurons, indicative of their evolutionarily conserved function.
Interface-induced sign reversal of the anomalous Hall effect in magnetic topological insulator heterostructures
Authors: Wang Fei , Wang Xuepeng , Zhao Yi-Fan , Xiao Di , Zhou Ling-Jie , Liu Wei , Zhang Zhidong , Zhao Weiwei , Chan Moses H. W. , Samarth Nitin , Liu Chaoxing , Zhang Haijun , Chang Cui-Zu 
Published: January 2021

AbstractThe Berry phase picture provides important insights into the electronic properties of condensed matter systems. The intrinsic anomalous Hall (AH) effect can be understood as the consequence of non-zero Berry curvature in momentum space. Here, we fabricate TI/magnetic TI heterostructures and find that the sign of the AH effect in the magnetic TI layer can be changed from being positive to negative with increasing the thickness of the top TI layer. Our first-principles calculations show that the built-in electric fields at the TI/magnetic TI interface influence the band structure of the magnetic TI layer, and thus lead to a reconstruction of the Berry curvature in the heterostructure samples. Based on the interface-induced AH effect with a negative sign in TI/V-doped TI bilayer structures, we create an artificial “topological Hall effect”-like feature in the Hall trace of the V-doped TI/TI/Cr-doped TI sandwich heterostructures. Our study provides a new route to create the Berry curvature change in magnetic topological materials that may lead to potential technological applications.
ZBP1 promotes LPS-induced cell death and IL-1β release via RHIM-mediated interactions with RIPK1
Authors: Muendlein Hayley I. , Connolly Wilson M. , Magri Zoie , Smirnova Irina , Ilyukha Vladimir , Gautam Avishekh , Degterev Alexei , Poltorak Alexander 
Published: January 2021

AbstractInflammation and cell death are closely linked arms of the host immune response to infection, which when carefully balanced ensure host survival. One example of this balance is the tightly regulated transition from TNFR1-associated pro-inflammatory complex I to pro-death complex II. By contrast, here we show that a TRIF-dependent complex containing FADD, RIPK1 and caspase-8 (that we have termed the TRIFosome) mediates cell death in response to Yersinia pseudotuberculosis and LPS. Furthermore, we show that constitutive binding between ZBP1 and RIPK1 is essential for the initiation of TRIFosome interactions, caspase-8-mediated cell death and inflammasome activation, thus positioning ZBP1 as an effector of cell death in the context of bacterial blockade of pro-inflammatory signaling. Additionally, our findings offer an alternative to the TNFR1-dependent model of complex II assembly, by demonstrating pro-death complex formation reliant on TRIF signaling.
The vortex-driven dynamics of droplets within droplets
Authors: Tiribocchi A. , Montessori A. , Lauricella M. , Bonaccorso F. , Succi S. , Aime S. , Milani M. , Weitz D. A. 
Published: January 2021

AbstractUnderstanding the fluid-structure interaction is crucial for an optimal design and manufacturing of soft mesoscale materials. Multi-core emulsions are a class of soft fluids assembled from cluster configurations of deformable oil-water double droplets (cores), often employed as building-blocks for the realisation of devices of interest in bio-technology, such as drug-delivery, tissue engineering and regenerative medicine. Here, we study the physics of multi-core emulsions flowing in microfluidic channels and report numerical evidence of a surprisingly rich variety of driven non-equilibrium states (NES), whose formation is caused by a dipolar fluid vortex triggered by the sheared structure of the flow carrier within the microchannel. The observed dynamic regimes range from long-lived NES at low core-area fraction, characterised by a planetary-like motion of the internal drops, to short-lived ones at high core-area fraction, in which a pre-chaotic motion results from multi-body collisions of inner drops, as combined with self-consistent hydrodynamic interactions. The onset of pre-chaotic behavior is marked by transitions of the cores from one vortex to another, a process that we interpret as manifestations of the system to maximize its entropy by filling voids, as they arise dynamically within the capsule.
Programmable phase-change metasurfaces on waveguides for multimode photonic convolutional neural network
Authors: Wu Changming , Yu Heshan , Lee Seokhyeong , Peng Ruoming , Takeuchi Ichiro , Li Mo 
Published: January 2021

AbstractNeuromorphic photonics has recently emerged as a promising hardware accelerator, with significant potential speed and energy advantages over digital electronics for machine learning algorithms, such as neural networks of various types. Integrated photonic networks are particularly powerful in performing analog computing of matrix-vector multiplication (MVM) as they afford unparalleled speed and bandwidth density for data transmission. Incorporating nonvolatile phase-change materials in integrated photonic devices enables indispensable programming and in-memory computing capabilities for on-chip optical computing. Here, we demonstrate a multimode photonic computing core consisting of an array of programable mode converters based on on-waveguide metasurfaces made of phase-change materials. The programmable converters utilize the refractive index change of the phase-change material Ge2Sb2Te5 during phase transition to control the waveguide spatial modes with a very high precision of up to 64 levels in modal contrast. This contrast is used to represent the matrix elements, with 6-bit resolution and both positive and negative values, to perform MVM computation in neural network algorithms. We demonstrate a prototypical optical convolutional neural network that can perform image processing and recognition tasks with high accuracy. With a broad operation bandwidth and a compact device footprint, the demonstrated multimode photonic core is promising toward large-scale photonic neural networks with ultrahigh computation throughputs.
Universal and tunable liquid–liquid separation by nanoparticle-embedded gating membranes based on a self-defined interfacial parameter
Authors: Li Xiangyu , Liu Jingjing , Qu Ruixiang , Zhang Weifeng , Liu Yanan , Zhai Huajun , Wei Yen , Hu Hanshi , Feng Lin 
Published: January 2021

AbstractSuperwetting porous membranes with tunable liquid repellency are highly desirable in broad domains including scientific research, chemical industry, and environmental protection. Such membranes should allow for controllable droplet bouncing or spreading, which is difficult to achieve for low surface energy organic liquids (OLs). Here we develop an interfacial physical parameter to regulate the OL wettability of nanoparticle-embedded membranes by structuring synergistic layers with reconfigurable surface energy components. Under the tunable solid-liquid interaction in the aggregation-induced process, the membranes demonstrate positive/negative liquid gating regularity for polar protic liquids, polar aprotic liquids, and nonpolar liquids. Such a membrane can be employed as self-adaptive gating for various immiscible liquid mixtures with superior separation efficiency and permeation flux, even afford successive achievement of high-performance in situ extraction-back extraction coupling. This study should provide distinctive insights into intrinsic wetting behaviors and have pioneered a rational strategy to design high-performance separation materials for diverse applications.