bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultra-bright Raman dots for multiplexed optical imaging
Authors: Zhao Zhilun , Chen Chen , Wei Shixuan , Xiong Hanqing , Hu Fanghao , Miao Yupeng , Jin Tianwei , Min Wei 
Published: February 2021

AbstractImaging the spatial distribution of biomolecules is at the core of modern biology. The development of fluorescence techniques has enabled researchers to investigate subcellular structures with nanometer precision. However, multiplexed imaging, i.e. observing complex biological networks and interactions, is mainly limited by the fundamental ‘spectral crowding’ of fluorescent materials. Raman spectroscopy-based methods, on the other hand, have a much greater spectral resolution, but often lack the required sensitivity for practical imaging of biomarkers. Addressing the pressing need for new Raman probes, herein we present a series of Raman-active nanoparticles (Rdots) that exhibit the combined advantages of ultra-brightness and compact sizes (~20 nm). When coupled with the emerging stimulated Raman scattering (SRS) microscopy, these Rdots are brighter than previously reported Raman-active organic probes by two to three orders of magnitude. We further obtain evidence supporting for SRS imaging of Rdots at single particle level. The compact size and ultra-brightness of Rdots allows immunostaining of specific protein targets (including cytoskeleton and low-abundant surface proteins) in mammalian cells and tissue slices with high imaging contrast. These Rdots thus offer a promising tool for a large range of studies on complex biological networks.
Ultrarobust, tough and highly stretchable self-healing materials based on cartilage-inspired noncovalent assembly nanostructure
Authors: Wang Yuyan , Huang Xin , Zhang Xinxing 
Published: February 2021

AbstractSelf-healing materials integrated with excellent mechanical strength and simultaneously high healing efficiency would be of great use in many fields, however their fabrication has been proven extremely challenging. Here, inspired by biological cartilage, we present an ultrarobust self-healing material by incorporating high density noncovalent bonds at the interfaces between the dentritic tannic acid-modified tungsten disulfide nanosheets and polyurethane matrix to collectively produce a strong interfacial interaction. The resultant nanocomposite material with interwoven network shows excellent tensile strength (52.3 MPa), high toughness (282.7 MJ m‒3, which is 1.6 times higher than spider silk and 9.4 times higher than metallic aluminum), high stretchability (1020.8%) and excellent healing efficiency (80–100%), which overturns the previous understanding of traditional noncovalent bonding self-healing materials where high mechanical robustness and healing ability are mutually exclusive. Moreover, the interfacical supramolecular crosslinking structure enables the functional-healing ability of the resultant flexible smart actuation devices. This work opens an avenue toward the development of ultrarobust self-healing materials for various flexible functional devices.
Comprehensive analysis of single cell ATAC-seq data with SnapATAC
Authors: Fang Rongxin , Preissl Sebastian , Li Yang , Hou Xiaomeng , Lucero Jacinta , Wang Xinxin , Motamedi Amir , Shiau Andrew K. , Zhou Xinzhu , Xie Fangming , Mukamel Eran A. , Zhang Kai , Zhang Yanxiao , Behrens M. Margarita , Ecker Joseph R. , Ren Bing 
Published: February 2021

AbstractIdentification of the cis-regulatory elements controlling cell-type specific gene expression patterns is essential for understanding the origin of cellular diversity. Conventional assays to map regulatory elements via open chromatin analysis of primary tissues is hindered by sample heterogeneity. Single cell analysis of accessible chromatin (scATAC-seq) can overcome this limitation. However, the high-level noise of each single cell profile and the large volume of data pose unique computational challenges. Here, we introduce SnapATAC, a software package for analyzing scATAC-seq datasets. SnapATAC dissects cellular heterogeneity in an unbiased manner and map the trajectories of cellular states. Using the Nyström method, SnapATAC can process data from up to a million cells. Furthermore, SnapATAC incorporates existing tools into a comprehensive package for analyzing single cell ATAC-seq dataset. As demonstration of its utility, SnapATAC is applied to 55,592 single-nucleus ATAC-seq profiles from the mouse secondary motor cortex. The analysis reveals ~370,000 candidate regulatory elements in 31 distinct cell populations in this brain region and inferred candidate cell-type specific transcriptional regulators.
Evaporation-driven transport-control of small molecules along nanoslits
Authors: Seo Sangjin , Ha Dogyeong , Kim Taesung 
Published: February 2021

AbstractUnderstanding and controlling the transport mechanisms of small molecules at the micro/nanoscales is vital because they provide a working principle for a variety of practical micro/nanofluidic applications. However, most precedent mechanisms still have remaining obstacles such as complicated fabrication processes, limitations of materials, and undesired damage on samples. Herein, we present the evaporation-driven transport-control of small molecules in gas-permeable and low-aspect ratio nanoslits, wherein both the diffusive and advective mass transports of solutes are affected by solvent evaporation through the nanoslit walls. The effect of the evaporation flux on the mass transport of small molecules in various nanoslit-integrated micro/nanofluidic devices is characterized, and dynamic transport along the nanoslit is investigated by conducting numerical simulations using the advection-diffusion equation. We further demonstrate that evaporation-driven, nanoslit-based transport-control can be easily applied to a micro/nanofluidic channel network in an independent and addressable array, offering a unique working principle for micro/nanofluidic applications and components such as molecule-valves, -concentrators, -pumps, and -filters.
Ecology-guided prediction of cross-feeding interactions in the human gut microbiome
Authors: Goyal Akshit , Wang Tong , Dubinkina Veronika , Maslov Sergei 
Published: February 2021

AbstractUnderstanding a complex microbial ecosystem such as the human gut microbiome requires information about both microbial species and the metabolites they produce and secrete. These metabolites are exchanged via a large network of cross-feeding interactions, and are crucial for predicting the functional state of the microbiome. However, till date, we only have information for a part of this network, limited by experimental throughput. Here, we propose an ecology-based computational method, GutCP, using which we predict hundreds of new experimentally untested cross-feeding interactions in the human gut microbiome. GutCP utilizes a mechanistic model of the gut microbiome with the explicit exchange of metabolites and their effects on the growth of microbial species. To build GutCP, we combine metagenomic and metabolomic measurements from the gut microbiome with optimization techniques from machine learning. Close to 65% of the cross-feeding interactions predicted by GutCP are supported by evidence from genome annotations, which we provide for experimental testing. Our method has the potential to greatly improve existing models of the human gut microbiome, as well as our ability to predict the metabolic profile of the gut.
A molecular quantitative trait locus map for osteoarthritis
Authors: Steinberg Julia , Southam Lorraine , Roumeliotis Theodoros I. , Clark Matthew J. , Jayasuriya Raveen L. , Swift Diane , Shah Karan M. , Butterfield Natalie C. , Brooks Roger A. , McCaskie Andrew W. , Bassett J. H. Duncan , Williams Graham R. , Choudhary Jyoti S. , Wilkinson J. Mark , Zeggini Eleftheria 
Published: February 2021

AbstractOsteoarthritis causes pain and functional disability for over 500 million people worldwide. To develop disease-stratifying tools and modifying therapies, we need a better understanding of the molecular basis of the disease in relevant tissue and cell types. Here, we study primary cartilage and synovium from 115 patients with osteoarthritis to construct a deep molecular signature map of the disease. By integrating genetics with transcriptomics and proteomics, we discover molecular trait loci in each tissue type and omics level, identify likely effector genes for osteoarthritis-associated genetic signals and highlight high-value targets for drug development and repurposing. These findings provide insights into disease aetiopathology, and offer translational opportunities in response to the global clinical challenge of osteoarthritis.
METTL3-dependent m6A modification programs T follicular helper cell differentiation
Authors: Yao Yingpeng , Yang Ying , Guo Wenhui , Xu Lifan , You Menghao , Zhang Yi-Chang , Sun Zhen , Cui Xiao , Yu Guotao , Qi Zhihong , Liu Jingjing , Wang Fang , Liu Juanjuan , Zhao Tianyan , Ye Lilin , Yang Yun-Gui , Yu Shuyang 
Published: February 2021

AbstractT follicular helper (TFH) cells are specialized effector CD4+ T cells critical to humoral immunity. Whether post-transcriptional regulation has a function in TFH cells is unknown. Here, we show conditional deletion of METTL3 (a methyltransferase catalyzing mRNA N6-methyladenosine (m6A) modification) in CD4+ T cells impairs TFH differentiation and germinal center responses in a cell-intrinsic manner in mice. METTL3 is necessary for expression of important TFH signature genes, including Tcf7, Bcl6, Icos and Cxcr5 and these effects depend on intact methyltransferase activity. m6A-miCLIP-seq shows the 3′ UTR of Tcf7 mRNA is subjected to METTL3-dependent m6A modification. Loss of METTL3 or mutation of the Tcf7 3′ UTR m6A site results in accelerated decay of Tcf7 transcripts. Importantly, ectopic expression of TCF-1 (encoded by Tcf7) rectifies TFH defects owing to METTL3 deficiency. Our findings indicate that METTL3 stabilizes Tcf7 transcripts via m6A modification to ensure activation of a TFH transcriptional program, indicating a pivotal function of post-transcriptional regulation in promoting TFH cell differentiation.
Nanoengineered chiral Pt-Ir alloys for high-performance enantioselective electrosynthesis
Authors: Butcha Sopon , Assavapanumat Sunpet , Ittisanronnachai Somlak , Lapeyre Veronique , Wattanakit Chularat , Kuhn Alexander 
Published: February 2021

AbstractThe design of efficient chiral catalysts is of crucial importance since it allows generating enantiomerically pure compounds. Tremendous efforts have been made over the past decades regarding the development of materials with enantioselective properties for various potential applications ranging from sensing to catalysis and separation. Recently, chiral features have been generated in mesoporous metals. Although these monometallic matrices show interesting enantioselectivity, they suffer from rather low stability, constituting an important roadblock for applications. Here, a straightforward strategy to circumvent this limitation by using nanostructured platinum-iridium alloys is presented. These materials can be successfully encoded with chiral information by co-electrodeposition from Pt and Ir salts in the simultaneous presence of a chiral compound and a lyotropic liquid crystal as asymmetric template and mesoporogen, respectively. The alloys enable a remarkable discrimination between chiral compounds and greatly improved enantioselectivity when used for asymmetric electrosynthesis (>95 %ee), combined with high electrochemical stability.
Retroviral integrations contribute to elevated host cancer rates during germline invasion
Authors: McEwen Gayle K. , Alquezar-Planas David E. , Dayaram Anisha , Gillett Amber , Tarlinton Rachael , Mongan Nigel , Chappell Keith J. , Henning Joerg , Tan Milton , Timms Peter , Young Paul R. , Roca Alfred L. , Greenwood Alex D. 
Published: February 2021

AbstractRepeated retroviral infections of vertebrate germlines have made endogenous retroviruses ubiquitous features of mammalian genomes. However, millions of years of evolution obscure many of the immediate repercussions of retroviral endogenisation on host health. Here we examine retroviral endogenisation during its earliest stages in the koala (Phascolarctos cinereus), a species undergoing germline invasion by koala retrovirus (KoRV) and affected by high cancer prevalence. We characterise KoRV integration sites (IS) in tumour and healthy tissues from 10 koalas, detecting 1002 unique IS, with hotspots of integration occurring in the vicinity of known cancer genes. We find that tumours accumulate novel IS, with proximate genes over-represented for cancer associations. We detect dysregulation of genes containing IS and identify a highly-expressed transduced oncogene. Our data provide insights into the tremendous mutational load suffered by the host during active retroviral germline invasion, a process repeatedly experienced and overcome during the evolution of vertebrate lineages.
Ultracold atom interferometry in space
Authors: Lachmann Maike D. , Ahlers Holger , Becker Dennis , Dinkelaker Aline N. , Grosse Jens , Hellmig Ortwin , Müntinga Hauke , Schkolnik Vladimir , Seidel Stephan T. , Wendrich Thijs , Wenzlawski André , Carrick Benjamin , Gaaloul Naceur , Lüdtke Daniel , Braxmaier Claus , Ertmer Wolfgang , Krutzik Markus , Lämmerzahl Claus , Peters Achim , Schleich Wolfgang P. , Sengstock Klaus , Wicht Andreas , Windpassinger Patrick , Rasel Ernst M. 
Published: February 2021

AbstractBose-Einstein condensates (BECs) in free fall constitute a promising source for space-borne interferometry. Indeed, BECs enjoy a slowly expanding wave function, display a large spatial coherence and can be engineered and probed by optical techniques. Here we explore matter-wave fringes of multiple spinor components of a BEC released in free fall employing light-pulses to drive Bragg processes and induce phase imprinting on a sounding rocket. The prevailing microgravity played a crucial role in the observation of these interferences which not only reveal the spatial coherence of the condensates but also allow us to measure differential forces. Our work marks the beginning of matter-wave interferometry in space with future applications in fundamental physics, navigation and earth observation.
Oscillations of Delta-like1 regulate the balance between differentiation and maintenance of muscle stem cells
Authors: Zhang Yao , Lahmann Ines , Baum Katharina , Shimojo Hiromi , Mourikis Philippos , Wolf Jana , Kageyama Ryoichiro , Birchmeier Carmen 
Published: February 2021

AbstractCell-cell interactions mediated by Notch are critical for the maintenance of skeletal muscle stem cells. However, dynamics, cellular source and identity of functional Notch ligands during expansion of the stem cell pool in muscle growth and regeneration remain poorly characterized. Here we demonstrate that oscillating Delta-like 1 (Dll1) produced by myogenic cells is an indispensable Notch ligand for self-renewal of muscle stem cells in mice. Dll1 expression is controlled by the Notch target Hes1 and the muscle regulatory factor MyoD. Consistent with our mathematical model, our experimental analyses show that Hes1 acts as the oscillatory pacemaker, whereas MyoD regulates robust Dll1 expression. Interfering with Dll1 oscillations without changing its overall expression level impairs self-renewal, resulting in premature differentiation of muscle stem cells during muscle growth and regeneration. We conclude that the oscillatory Dll1 input into Notch signaling ensures the equilibrium between self-renewal and differentiation in myogenic cell communities.
VPS34 K29/K48 branched ubiquitination governed by UBE3C and TRABID regulates autophagy, proteostasis and liver metabolism
Authors: Chen Yu-Hsuan , Huang Tzu-Yu , Lin Yu-Tung , Lin Shu-Yu , Li Wen-Hsin , Hsiao Hsiang-Jung , Yan Ruei-Liang , Tang Hong-Wen , Shen Zhao-Qing , Chen Guang-Chao , Wu Kuen-Phon , Tsai Ting-Fen , Chen Ruey-Hwa 
Published: February 2021

AbstractThe ubiquitin–proteasome system (UPS) and autophagy are two major quality control processes whose impairment is linked to a wide variety of diseases. The coordination between UPS and autophagy remains incompletely understood. Here, we show that ubiquitin ligase UBE3C and deubiquitinating enzyme TRABID reciprocally regulate K29/K48-branched ubiquitination of VPS34. We find that this ubiquitination enhances the binding of VPS34 to proteasomes for degradation, thereby suppressing autophagosome formation and maturation. Under ER and proteotoxic stresses, UBE3C recruitment to phagophores is compromised with a concomitant increase of its association with proteasomes. This switch attenuates the action of UBE3C on VPS34, thereby elevating autophagy activity to facilitate proteostasis, ER quality control and cell survival. Specifically in the liver, we show that TRABID-mediated VPS34 stabilization is critical for lipid metabolism and is downregulated during the pathogenesis of steatosis. This study identifies a ubiquitination type on VPS34 and elucidates its cellular fate and physiological functions in proteostasis and liver metabolism.
The atomistic details of the ice recrystallisation inhibition activity of PVA
Authors: Bachtiger Fabienne , Congdon Thomas R. , Stubbs Christopher , Gibson Matthew I. , Sosso Gabriele C. 
Published: February 2021

AbstractUnderstanding the ice recrystallisation inhibition (IRI) activity of antifreeze biomimetics is crucial to the development of the next generation of cryoprotectants. In this work, we bring together molecular dynamics simulations and quantitative experimental measurements to unravel the microscopic origins of the IRI activity of poly(vinyl)alcohol (PVA)—the most potent of biomimetic IRI agents. Contrary to the emerging consensus, we find that PVA does not require a “lattice matching” to ice in order to display IRI activity: instead, it is the effective volume of PVA and its contact area with the ice surface which dictates its IRI strength. We also find that entropic contributions may play a role in the ice-PVA interaction and we demonstrate that small block co-polymers (up to now thought to be IRI-inactive) might display significant IRI potential. This work clarifies the atomistic details of the IRI activity of PVA and provides novel guidelines for the rational design of cryoprotectants.
Experimental demonstration of entanglement-enabled universal quantum cloning in a circuit
Authors: Yang Zhen-Biao , Han Pei-Rong , Huang Xin-Jie , Ning Wen , Li Hekang , Xu Kai , Zheng Dongning , Fan Heng , Zheng Shi-Biao 
Published: February 2021

AbstractNo-cloning theorem forbids perfect cloning of an unknown quantum state. A universal quantum cloning machine (UQCM), capable of producing two copies of any input qubit with the optimal fidelity, is of fundamental interest and has applications in quantum information processing. This is enabled by delicately tailored nonclassical correlations between the input qubit and the copying qubits, which distinguish the UQCM from a classical counterpart, but whose experimental demonstrations are still lacking. We here implement the UQCM in a superconducting circuit and investigate these correlations. The measured entanglements well agree with our theoretical prediction that they are independent of the input state and thus constitute a universal quantum behavior of the UQCM that was not previously revealed. Another feature of our experiment is the realization of deterministic and individual cloning, in contrast to previously demonstrated UQCMs, which either were probabilistic or did not constitute true cloning of individual qubits.
DNA hydrolysing IgG catalytic antibodies: an emerging link between psychoses and autoimmunity
Authors: Ramesh Rajendran , Sundaresh Aparna , Rajkumar Ravi Philip , Negi Vir Singh , Vijayalakshmi M. A. , Krishnamoorthy Rajagopal , Tamouza Ryad , Leboyer Marion , Kamalanathan A. S. 
Published: February 2021

AbstractIt is not uncommon to observe autoimmune comorbidities in a significant subset of patients with psychotic disorders, namely schizophrenia (SCZ) and bipolar disorder (BPD). To understand the autoimmune basis, the DNA abyzme activity mediated by serum polyclonal IgG Abs were examined in psychoses patients, quantitatively, by an in-house optimized DNase assay. A similar activity exhibited by IgG Abs from neuropsychiatric-systemic lupus erythematosus (NP-SLE) patients was used as a comparator. Our data revealed that the IgG DNase activity of SCZ was close to that of NP-SLE and it was twofold higher than the healthy controls. Interestingly, the association between DNase activity with PANSS (positive, general and total scores) and MADRS were noted in a subgroup of SCZ and BPD patients, respectively. In our study group, the levels of IL-6 and total IgG in BPD patients were higher than SCZ and healthy controls, indicating a relatively inflammatory nature in BPD, while autoimmune comorbidity was mainly observed in SCZ patients.
Highly pathogenic avian influenza A/Guangdong/17SF003/2016 is immunogenic and induces cross-protection against antigenically divergent H7N9 viruses
Authors: Radvak Peter , Kosikova Martina , Kuo Yuan-Chia , Li Xing , Garner Richard , Schmeisser Falko , Kosik Ivan , Ye Zhiping , Weir Jerry P. , Yewdell Jonathan W. , Xie Hang 
Published: February 2021

AbstractAvian influenza A(H7N9) epidemics have a fatality rate of approximately 40%. Previous studies reported that low pathogenic avian influenza (LPAI)-derived candidate vaccine viruses (CVVs) are poorly immunogenic. Here, we assess the immunogenicity and efficacy of a highly pathogenic avian influenza (HPAI) A/Guangdong/17SF003/2016 (GD/16)-extracted hemagglutinin (eHA) vaccine. GD/16 eHA induces robust H7-specific antibody responses in mice with a marked adjuvant antigen-sparing effect. Mice immunized with adjuvanted GD/16 eHA are protected from the lethal LPAI and HPAI H7N9 challenges, in stark contrast to low antibody titers and high mortality in mice receiving adjuvanted LPAI H7 eHAs. The protection correlates well with the magnitude of the H7-specific antibody response (IgG and microneutralization) or HA group 2 stem-specific IgG. Inclusion of adjuvanted GD/16 eHA in heterologous prime-boost improves the immunogenicity and protection of LPAI H7 HAs in mice. Our findings support the inclusion of GD/16-derived CVV in the pandemic preparedness vaccine stockpile.
High-resolution surface faulting from the 1983 Idaho Lost River Fault Mw 6.9 earthquake and previous events
Authors: Bello Simone , Scott Chelsea P. , Ferrarini Federica , Brozzetti Francesco , Scott Tyler , Cirillo Daniele , de Nardis Rita , Arrowsmith J Ramón , Lavecchia Giusy 
Published: February 2021

AbstractWe present high-resolution mapping and surface faulting measurements along the Lost River fault (Idaho-USA), a normal fault activated in the 1983 (Mw6.9) earthquake. The earthquake ruptured ~35 km of the fault with a maximum throw of ~3 m. From new 5 to 30 cm-pixel resolution topography collected by an Unmanned Aerial Vehicle, we produce the most comprehensive dataset of systematically measured vertical separations from ~37 km of fault length activated by the 1983 and prehistoric earthquakes. We provide Digital Elevation Models, orthophotographs, and three tables of: (i) 757 surface rupture traces, (ii) 1295 serial topographic profiles spaced 25 m apart that indicate rupture zone width and (iii) 2053 vertical separation measurements, each with additional textual and numerical fields. Our novel dataset supports advancing scientific knowledge about this fault system, refining scaling laws of intra-continental faults, comparing to other earthquakes to better understand faulting processes, and contributing to global probabilistic hazard approaches. Our methodology can be applied to other fault zones with high-resolution topographic data.