bluuebunny/crossref_metadata_2025 huggingface dataset:
Rosuvastatin protects against coronary microembolization-induced cardiac injury via inhibiting NLRP3 inflammasome activation
Authors: Chen Ao , Chen Zhangwei , Zhou You , Wu Yuan , Xia Yan , Lu Danbo , Fan Mengkang , Li Su , Chen Jinxiang , Sun Aijun , Zou Yunzeng , Qian Juying , Ge Junbo
Published: January 2021

Coronary microembolization (CME), a common reason for periprocedural myocardial infarction (PMI), bears very important prognostic implications. However, the molecular mechanisms related to CME remain largely elusive. Statins have been shown to prevent PMI, but the underlying mechanism has not been identified. Here, we examine whether the NLRP3 inflammasome contributes to CME-induced cardiac injury and investigate the effects of statin therapy on CME. In vivo study, mice with CME were treated with 40 mg/kg/d rosuvastatin (RVS) orally or a selective NLRP3 inflammasome inhibitor MCC950 intraperitoneally (20 mg/kg/d). Mice treated with MCC950 and RVS showed improved cardiac contractile function and morphological changes, diminished fibrosis and microinfarct size, and reduced serum lactate dehydrogenase (LDH) level. Mechanistically, RVS decreased the expression of NLRP3, caspase-1, interleukin-1β, and Gasdermin D N-terminal domains. Proteomics analysis revealed that RVS restored the energy metabolism and oxidative phosphorylation in CME. Furthermore, reduced reactive oxygen species (ROS) level and alleviated mitochondrial damage were observed in RVS-treated mice. In vitro study, RVS inhibited the activation of NLRP3 inflammasome induced by tumor necrosis factor α plus hypoxia in H9c2 cells. Meanwhile, the pyroptosis was also suppressed by RVS, indicated by the increased cell viability, decreased LDH and propidium iodide uptake in H9c2 cells. RVS also reduced the level of mitochondrial ROS generation in vitro. Our results indicate the NLRP3 inflammasome-dependent cardiac pyroptosis plays an important role in CME-induced cardiac injury and its inhibitor exerts cardioprotective effect following CME. We also uncover the anti-pyroptosis role of RVS in CME, which is associated with regulating mitochondrial ROS.
Experimental evidence for scale-induced category convergence across populations
Authors: Guilbeault Douglas , Baronchelli Andrea , Centola Damon
Published: January 2021

Individuals vary widely in how they categorize novel and ambiguous phenomena. This individual variation has led influential theories in cognitive and social science to suggest that communication in large social groups introduces path dependence in category formation, which is expected to lead separate populations toward divergent cultural trajectories. Yet, anthropological data indicates that large, independent societies consistently arrive at highly similar category systems across a range of topics. How is it possible for diverse populations, consisting of individuals with significant variation in how they categorize the world, to independently construct similar category systems? Here, we investigate this puzzle experimentally by creating an online “Grouping Game” in which we observe how people in small and large populations collaboratively construct category systems for a continuum of ambiguous stimuli. We find that solitary individuals and small groups produce highly divergent category systems; however, across independent trials with unique participants, large populations consistently converge on highly similar category systems. A formal model of critical mass dynamics in social networks accurately predicts this process of scale-induced category convergence. Our findings show how large communication networks can filter lexical diversity among individuals to produce replicable society-level patterns, yielding unexpected implications for cultural evolution.
Friendship stability in adolescence is associated with ventral striatum responses to vicarious rewards
Authors: Schreuders Elisabeth , Braams Barbara R. , Crone Eveline A. , Güroğlu Berna
Published: January 2021

An important task for adolescents is to form and maintain friendships. In this three-wave biannual study, we used a longitudinal neuroscience perspective to examine the dynamics of friendship stability. Relative to childhood and adulthood, adolescence is marked by elevated ventral striatum activity when gaining self-serving rewards. Using a sample of participants between the ages of eight and twenty-eight, we tested age-related changes in ventral striatum response to gaining for stable (n = 48) versus unstable best friends (n = 75) (and self). In participants with stable friendships, we observed a quadratic developmental trajectory of ventral striatum responses to winning versus losing rewards for friends, whereas participants with unstable best friends showed no age-related changes. Ventral striatum activity in response to winning versus losing for friends further varied with friendship closeness for participants with unstable friendships. We suggest that these findings may reflect changing social motivations related to formation and maintenance of friendships across adolescence.
Multiplexed characterization of rationally designed promoter architectures deconstructs combinatorial logic for IPTG-inducible systems
Authors: Yu Timothy C. , Liu Winnie L. , Brinck Marcia S. , Davis Jessica E. , Shek Jeremy , Bower Grace , Einav Tal , Insigne Kimberly D. , Phillips Rob , Kosuri Sriram , Urtecho Guillaume
Published: January 2021

A crucial step towards engineering biological systems is the ability to precisely tune the genetic response to environmental stimuli. In the case of Escherichia coli inducible promoters, our incomplete understanding of the relationship between sequence composition and gene expression hinders our ability to predictably control transcriptional responses. Here, we profile the expression dynamics of 8269 rationally designed, IPTG-inducible promoters that collectively explore the individual and combinatorial effects of RNA polymerase and LacI repressor binding site strengths. We then fit a statistical mechanics model to measured expression that accurately models gene expression and reveals properties of theoretically optimal inducible promoters. Furthermore, we characterize three alternative promoter architectures and show that repositioning binding sites within promoters influences the types of combinatorial effects observed between promoter elements. In total, this approach enables us to deconstruct relationships between inducible promoter elements and discover practical insights for engineering inducible promoters with desirable characteristics.
Mechanisms of muscle atrophy and hypertrophy: implications in health and disease
Authors: Sartori Roberta , Romanello Vanina , Sandri Marco
Published: January 2021

Skeletal muscle is the protein reservoir of our body and an important regulator of glucose and lipid homeostasis. Consequently, the growth or the loss of muscle mass can influence general metabolism, locomotion, eating and respiration. Therefore, it is not surprising that excessive muscle loss is a bad prognostic index of a variety of diseases ranging from cancer, organ failure, infections and unhealthy ageing. Muscle function is influenced by different quality systems that regulate the function of contractile proteins and organelles. These systems are controlled by transcriptional dependent programs that adapt muscle cells to environmental and nutritional clues. Mechanical, oxidative, nutritional and energy stresses, as well as growth factors or cytokines modulate signaling pathways that, ultimately, converge on protein and organelle turnover. Novel insights that control and orchestrate such complex network are continuously emerging and will be summarized in this review. Understanding the mechanisms that control muscle mass will provide therapeutic targets for the treatment of muscle loss in inherited and non-hereditary diseases and for the improvement of the quality of life during ageing.
Estimating internationally imported cases during the early COVID-19 pandemic
Authors: Menkir Tigist F. , Chin Taylor , Hay James A. , Surface Erik D. , De Salazar Pablo M. , Buckee Caroline O. , Watts Alexander , Khan Kamran , Sherbo Ryan , Yan Ada W. C. , Mina Michael J. , Lipsitch Marc , Niehus Rene
Published: January 2021

Early in the COVID-19 pandemic, predictions of international outbreaks were largely based on imported cases from Wuhan, China, potentially missing imports from other cities. We provide a method, combining daily COVID-19 prevalence and flight passenger volume, to estimate importations from 18 Chinese cities to 43 international destinations, including 26 in Africa. Global case importations from China in early January came primarily from Wuhan, but the inferred source shifted to other cities in mid-February, especially for importations to African destinations. We estimate that 10.4 (6.2 – 27.1) COVID-19 cases were imported to these African destinations, which exhibited marked variation in their magnitude and main sources of importation. We estimate that 90% of imported cases arrived between 17 January and 7 February, prior to the first case detections. Our results highlight the dynamic role of source locations, which can help focus surveillance and response efforts.
Genome-wide analyses of behavioural traits are subject to bias by misreports and longitudinal changes
Authors: Xue Angli , Jiang Longda , Zhu Zhihong , Wray Naomi R. , Visscher Peter M. , Zeng Jian , Yang Jian
Published: January 2021

Genome-wide association studies (GWAS) have discovered numerous genetic variants associated with human behavioural traits. However, behavioural traits are subject to misreports and longitudinal changes (MLC) which can cause biases in GWAS and follow-up analyses. Here, we demonstrate that individuals with higher disease burden in the UK Biobank (n = 455,607) are more likely to misreport or reduce their alcohol consumption levels, and propose a correction procedure to mitigate the MLC-induced biases. The alcohol consumption GWAS signals removed by the MLC corrections are enriched in metabolic/cardiovascular traits. Almost all the previously reported negative estimates of genetic correlations between alcohol consumption and common diseases become positive/non-significant after the MLC corrections. We also observe MLC biases for smoking and physical activities in the UK Biobank. Our findings provide a plausible explanation of the controversy about the effects of alcohol consumption on health outcomes and a caution for future analyses of self-reported behavioural traits in biobank data.
Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity
Authors: Fougeroux Cyrielle , Goksøyr Louise , Idorn Manja , Soroka Vladislav , Myeni Sebenzile K. , Dagil Robert , Janitzek Christoph M. , Søgaard Max , Aves Kara-Lee , Horsted Emma W. , Erdoğan Sayit Mahmut , Gustavsson Tobias , Dorosz Jerzy , Clemmensen Stine , Fredsgaard Laurits , Thrane Susan , Vidal-Calvo Elena E. , Khalifé Paul , Hulen Thomas M. , Choudhary Swati , Theisen Michael , Singh Susheel K. , Garcia-Senosiain Asier , Van Oosten Linda , Pijlman Gorben , Hierzberger Bettina , Domeyer Tanja , Nalewajek Blanka W. , Strøbæk Anette , Skrzypczak Magdalena , Andersson Laura F. , Buus Søren , Buus Anette Stryhn , Christensen Jan Pravsgaard , Dalebout Tim J. , Iversen Kasper , Harritshøj Lene H. , Mordmüller Benjamin , Ullum Henrik , Reinert Line S. , de Jongh Willem Adriaan , Kikkert Marjolein , Paludan Søren R. , Theander Thor G. , Nielsen Morten A. , Salanti Ali , Sander Adam F.
Published: January 2021

The rapid development of a SARS-CoV-2 vaccine is a global priority. Here, we develop two capsid-like particle (CLP)-based vaccines displaying the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. RBD antigens are displayed on AP205 CLPs through a split-protein Tag/Catcher, ensuring unidirectional and high-density display of RBD. Both soluble recombinant RBD and RBD displayed on CLPs bind the ACE2 receptor with nanomolar affinity. Mice are vaccinated with soluble RBD or CLP-displayed RBD, formulated in Squalene-Water-Emulsion. The RBD-CLP vaccines induce higher levels of serum anti-spike antibodies than the soluble RBD vaccines. Remarkably, one injection with our lead RBD-CLP vaccine in mice elicits virus neutralization antibody titers comparable to those found in patients that had recovered from COVID-19. Following booster vaccinations, the virus neutralization titers exceed those measured after natural infection, at serum dilutions above 1:10,000. Thus, the RBD-CLP vaccine is a highly promising candidate for preventing COVID-19.
Observations of pressure anisotropy effects within semi-collisional magnetized plasma bubbles
Authors: Tubman E. R. , Joglekar A. S. , Bott A. F. A. , Borghesi M. , Coleman B. , Cooper G. , Danson C. N. , Durey P. , Foster J. M. , Graham P. , Gregori G. , Gumbrell E. T. , Hill M. P. , Hodge T. , Kar S. , Kingham R. J. , Read M. , Ridgers C. P. , Skidmore J. , Spindloe C. , Thomas A. G. R. , Treadwell P. , Wilson S. , Willingale L. , Woolsey N. C.
Published: January 2021

Magnetized plasma interactions are ubiquitous in astrophysical and laboratory plasmas. Various physical effects have been shown to be important within colliding plasma flows influenced by opposing magnetic fields, however, experimental verification of the mechanisms within the interaction region has remained elusive. Here we discuss a laser-plasma experiment whereby experimental results verify that Biermann battery generated magnetic fields are advected by Nernst flows and anisotropic pressure effects dominate these flows in a reconnection region. These fields are mapped using time-resolved proton probing in multiple directions. Various experimental, modelling and analytical techniques demonstrate the importance of anisotropic pressure in semi-collisional, high-β plasmas, causing a reduction in the magnitude of the reconnecting fields when compared to resistive processes. Anisotropic pressure dynamics are crucial in collisionless plasmas, but are often neglected in collisional plasmas. We show pressure anisotropy to be essential in maintaining the interaction layer, redistributing magnetic fields even for semi-collisional, high energy density physics (HEDP) regimes.
A logical network-based drug-screening platform for Alzheimer’s disease representing pathological features of human brain organoids
Authors: Park Jong-Chan , Jang So-Yeong , Lee Dongjoon , Lee Jeongha , Kang Uiryong , Chang Hongjun , Kim Haeng Jun , Han Sun-Ho , Seo Jinsoo , Choi Murim , Lee Dong Young , Byun Min Soo , Yi Dahyun , Cho Kwang-Hyun , Mook-Jung Inhee
Published: January 2021

Developing effective drugs for Alzheimer’s disease (AD), the most common cause of dementia, has been difficult because of complicated pathogenesis. Here, we report an efficient, network-based drug-screening platform developed by integrating mathematical modeling and the pathological features of AD with human iPSC-derived cerebral organoids (iCOs), including CRISPR-Cas9-edited isogenic lines. We use 1300 organoids from 11 participants to build a high-content screening (HCS) system and test blood–brain barrier-permeable FDA-approved drugs. Our study provides a strategy for precision medicine through the convergence of mathematical modeling and a miniature pathological brain model using iCOs.
Nanoparticle delivery of microRNA-146a regulates mechanotransduction in lung macrophages and mitigates injury during mechanical ventilation
Authors: Bobba Christopher M. , Fei Qinqin , Shukla Vasudha , Lee Hyunwook , Patel Pragi , Putman Rachel K. , Spitzer Carleen , Tsai MuChun , Wewers Mark D. , Lee Robert J. , Christman John W. , Ballinger Megan N. , Ghadiali Samir N. , Englert Joshua A.
Published: January 2021

Mechanical ventilation generates injurious forces that exacerbate lung injury. These forces disrupt lung barrier integrity, trigger proinflammatory mediator release, and differentially regulate genes and non-coding oligonucleotides including microRNAs. In this study, we identify miR-146a as a mechanosensitive microRNA in alveolar macrophages that has therapeutic potential to mitigate lung injury during mechanical ventilation. We use humanized in-vitro systems, mouse models, and biospecimens from patients to elucidate the expression dynamics of miR-146a needed to decrease lung injury during mechanical ventilation. We find that the endogenous increase in miR-146a following injurious ventilation is not sufficient to prevent lung injury. However, when miR-146a is highly overexpressed using a nanoparticle delivery platform it is sufficient to prevent injury. These data indicate that the endogenous increase in microRNA-146a during mechanical ventilation is a compensatory response that partially limits injury and that nanoparticle delivery of miR-146a is an effective strategy for mitigating lung injury during mechanical ventilation.
isoCirc catalogs full-length circular RNA isoforms in human transcriptomes
Authors: Xin Ruijiao , Gao Yan , Gao Yuan , Wang Robert , Kadash-Edmondson Kathryn E. , Liu Bo , Wang Yadong , Lin Lan , Xing Yi
Published: January 2021

Circular RNAs (circRNAs) have emerged as an important class of functional RNA molecules. Short-read RNA sequencing (RNA-seq) is a widely used strategy to identify circRNAs. However, an inherent limitation of short-read RNA-seq is that it does not experimentally determine the full-length sequences and exact exonic compositions of circRNAs. Here, we report isoCirc, a strategy for sequencing full-length circRNA isoforms, using rolling circle amplification followed by nanopore long-read sequencing. We describe an integrated computational pipeline to reliably characterize full-length circRNA isoforms using isoCirc data. Using isoCirc, we generate a comprehensive catalog of 107,147 full-length circRNA isoforms across 12 human tissues and one human cell line (HEK293), including 40,628 isoforms ≥500 nt in length. We identify widespread alternative splicing events within the internal part of circRNAs, including 720 retained intron events corresponding to a class of exon-intron circRNAs (EIciRNAs). Collectively, isoCirc and the companion dataset provide a useful strategy and resource for studying circRNAs in human transcriptomes.
Biomass burning aerosols in most climate models are too absorbing
Authors: Brown Hunter , Liu Xiaohong , Pokhrel Rudra , Murphy Shane , Lu Zheng , Saleh Rawad , Mielonen Tero , Kokkola Harri , Bergman Tommi , Myhre Gunnar , Skeie Ragnhild B. , Watson-Paris Duncan , Stier Philip , Johnson Ben , Bellouin Nicolas , Schulz Michael , Vakkari Ville , Beukes Johan Paul , van Zyl Pieter Gideon , Liu Shang , Chand Duli
Published: January 2021

Uncertainty in the representation of biomass burning (BB) aerosol composition and optical properties in climate models contributes to a range in modeled aerosol effects on incoming solar radiation. Depending on the model, the top-of-the-atmosphere BB aerosol effect can range from cooling to warming. By relating aerosol absorption relative to extinction and carbonaceous aerosol composition from 12 observational datasets to nine state-of-the-art Earth system models/chemical transport models, we identify varying degrees of overestimation in BB aerosol absorptivity by these models. Modifications to BB aerosol refractive index, size, and mixing state improve the Community Atmosphere Model version 5 (CAM5) agreement with observations, leading to a global change in BB direct radiative effect of −0.07 W m−2, and regional changes of −2 W m−2 (Africa) and −0.5 W m−2 (South America/Temperate). Our findings suggest that current modeled BB contributes less to warming than previously thought, largely due to treatments of aerosol mixing state.
Widespread reworking of Hadean-to-Eoarchean continents during Earth’s thermal peak
Authors: Kirkland C. L. , Hartnady M. I. H. , Barham M. , Olierook H. K. H. , Steenfelt A. , Hollis J. A.
Published: January 2021

The nature and evolution of Earth’s crust during the Hadean and Eoarchean is largely unknown owing to a paucity of material preserved from this period. However, clues may be found in the chemical composition of refractory minerals that initially grew in primordial material but were subsequently incorporated into younger rocks and sediment during lithospheric reworking. Here we report Hf isotopic data in 3.9 to 1.8 billion year old detrital zircon from modern stream sediment samples from West Greenland, which document successive reworking of felsic Hadean-to-Eoarchean crust during subsequent periods of magmatism. Combined with global zircon Hf data, we show a planetary shift towards, on average, more juvenile Hf values 3.2 to 3.0 billion years ago. This crustal rejuvenation was coincident with peak mantle potential temperatures that imply greater degrees of mantle melting and injection of hot mafic-ultramafic magmas into older Hadean-to-Eoarchean felsic crust at this time. Given the repeated recognition of felsic Hadean-to-Eoarchean diluted signatures, ancient crust appears to have acted as buoyant life-rafts with enhanced preservation-potential that facilitated later rapid crustal growth during the Meso-and-Neoarchean.
The coupling and competition of crystallization and phase separation, correlating thermodynamics and kinetics in OPV morphology and performances
Authors: Wang Zaiyu , Gao Ke , Kan Yuanyuan , Zhang Ming , Qiu Chaoqun , Zhu Lei , Zhao Zhe , Peng Xiaobin , Feng Wei , Qian Zhiyuan , Gu Xiaodan , Jen Alex K.-Y. , Tang Ben Zhong , Cao Yong , Zhang Yongming , Liu Feng
Published: January 2021

The active layer morphology transition of organic photovoltaics under non-equilibrium conditions are of vital importance in determining the device power conversion efficiency and stability; however, a general and unified picture on this issue has not been well addressed. Using combined in situ and ex situ morphology characterizations, morphological parameters relating to kinetics and thermodynamics of morphology evolution are extracted and studied in model systems under thermal annealing. The coupling and competition of crystallization and demixing are found to be critical in morphology evolution, phase purification and interfacial orientation. A unified model summarizing different phase diagrams and all possible kinetic routes is proposed. The current observations address the fundamental issues underlying the formation of the complex multi-length scale morphology in bulk heterojunction blends and provide useful morphology optimization guidelines for processing devices with higher efficiency and stability.
Spontaneous sparse learning for PCM-based memristor neural networks
Authors: Lim Dong-Hyeok , Wu Shuang , Zhao Rong , Lee Jung-Hoon , Jeong Hongsik , Shi Luping
Published: January 2021

Neural networks trained by backpropagation have achieved tremendous successes on numerous intelligent tasks. However, naïve gradient-based training and updating methods on memristors impede applications due to intrinsic material properties. Here, we built a 39 nm 1 Gb phase change memory (PCM) memristor array and quantified the unique resistance drift effect. On this basis, spontaneous sparse learning (SSL) scheme that leverages the resistance drift to improve PCM-based memristor network training is developed. During training, SSL regards the drift effect as spontaneous consistency-based distillation process that reinforces the array weights at the high-resistance state continuously unless the gradient-based method switches them to low resistance. Experiments show that the SSL not only helps the convergence of network with better performance and sparsity controllability without additional computation in handwritten digit classification. This work promotes the learning algorithms with the intrinsic properties of memristor devices, opening a new direction for development of neuromorphic computing chips.
Unraveling fundamental active units in carbon nitride for photocatalytic oxidation reactions
Authors: Huang Chaofeng , Wen Yaping , Ma Jin , Dong Dandan , Shen Yanfei , Liu Songqin , Ma Haibo , Zhang Yuanjian
Published: January 2021

Covalently bonded carbon nitride (CN) has stimulated extensive attention as a metal-free semiconductor. However, because of the complexity of polymeric structures, the acquisition of critical roles of each molecular constituent in CN for photocatalysis remains elusive. Herein, we clarify the fundamental active units of CN in photocatalysis by synthesizing CN with more detailed molecular structures. Enabled by microwave synthesis, the as-prepared CN consists of distinguishable melem (M1) and its incomplete condensed form (M2). We disclose rather than the traditional opinion of being involved in the whole photocatalytic processes, M1 and M2 make primary contributions in light absorption and charge separation, respectively. Meanwhile, oxygen molecules are unusually observed to be activated by participating in the photoexcited processes via electronic coupling mainly to M2. As a result, such CN has a higher activity, which was up to 8 times that of traditional bulk CN for photocatalytic oxidation of tetracycline in water.
The molecular make up of smoldering myeloma highlights the evolutionary pathways leading to multiple myeloma
Authors: Boyle Eileen M. , Deshpande Shayu , Tytarenko Ruslana , Ashby Cody , Wang Yan , Bauer Michael A. , Johnson Sarah K. , Wardell Christopher P. , Thanendrarajan Sharmilan , Zangari Maurizio , Facon Thierry , Dumontet Charles , Barlogie Bart , Arbini Arnaldo , Rustad Even H. , Maura Francesco , Landgren Ola , Zhan Fenghuang , van Rhee Frits , Schinke Carolina , Davies Faith E. , Morgan Gareth J. , Walker Brian A.
Published: January 2021

Smoldering myeloma (SMM) is associated with a high-risk of progression to myeloma (MM). We report the results of a study of 82 patients with both targeted sequencing that included a capture of the immunoglobulin and MYC regions. By comparing these results to newly diagnosed myeloma (MM) we show fewer NRAS and FAM46C mutations together with fewer adverse translocations, del(1p), del(14q), del(16q), and del(17p) in SMM consistent with their role as drivers of the transition to MM. KRAS mutations are associated with a shorter time to progression (HR 3.5 (1.5–8.1), p = 0.001). In an analysis of change in clonal structure over time we studied 53 samples from nine patients at multiple time points. Branching evolutionary patterns, novel mutations, biallelic hits in crucial tumour suppressor genes, and segmental copy number changes are key mechanisms underlying the transition to MM, which can precede progression and be used to guide early intervention strategies.
Nickel isotopic evidence for late-stage accretion of Mercury-like differentiated planetary embryos
Authors: Wang Shui-Jiong , Wang Wenzhong , Zhu Jian-Ming , Wu Zhongqing , Liu Jingao , Han Guilin , Teng Fang-Zhen , Huang Shichun , Wu Hongjie , Wang Yujian , Wu Guangliang , Li Weihan
Published: January 2021

Earth’s habitability is closely tied to its late-stage accretion, during which impactors delivered the majority of life-essential volatiles. However, the nature of these final building blocks remains poorly constrained. Nickel (Ni) can be a useful tracer in characterizing this accretion as most Ni in the bulk silicate Earth (BSE) comes from the late-stage impactors. Here, we apply Ni stable isotope analysis to a large number of meteorites and terrestrial rocks, and find that the BSE has a lighter Ni isotopic composition compared to chondrites. Using first-principles calculations based on density functional theory, we show that core-mantle differentiation cannot produce the observed light Ni isotopic composition of the BSE. Rather, the sub-chondritic Ni isotopic signature was established during Earth’s late-stage accretion, probably through the Moon-forming giant impact. We propose that a highly reduced sulfide-rich, Mercury-like body, whose mantle is characterized by light Ni isotopic composition, collided with and merged into the proto-Earth during the Moon-forming giant impact, producing the sub-chondritic Ni isotopic signature of the BSE, while delivering sulfur and probably other volatiles to the Earth.
Electric-field control of skyrmions in multiferroic heterostructure via magnetoelectric coupling
Authors: Ba You , Zhuang Shihao , Zhang Yike , Wang Yutong , Gao Yang , Zhou Hengan , Chen Mingfeng , Sun Weideng , Liu Quan , Chai Guozhi , Ma Jing , Zhang Ying , Tian Huanfang , Du Haifeng , Jiang Wanjun , Nan Cewen , Hu Jia-Mian , Zhao Yonggang
Published: January 2021

Room-temperature skyrmions in magnetic multilayers are considered to be promising candidates for the next-generation spintronic devices. Several approaches have been developed to control skyrmions, but they either cause significant heat dissipation or require ultrahigh electric fields near the breakdown threshold. Here, we demonstrate electric-field control of skyrmions through strain-mediated magnetoelectric coupling in ferromagnetic/ferroelectric multiferroic heterostructures. We show the process of non-volatile creation of multiple skyrmions, reversible deformation and annihilation of a single skyrmion by performing magnetic force microscopy with in situ electric fields. Strain-induced changes in perpendicular magnetic anisotropy and interfacial Dzyaloshinskii–Moriya interaction strength are characterized experimentally. These experimental results, together with micromagnetic simulations, demonstrate that strain-mediated magnetoelectric coupling (via strain-induced changes in both the perpendicular magnetic anisotropy and interfacial Dzyaloshinskii–Moriya interaction is responsible for the observed electric-field control of skyrmions. Our work provides a platform to investigate electric-field control of skyrmions in multiferroic heterostructures and paves the way towards more energy-efficient skyrmion-based spintronics.
Spatially dispersing Yu-Shiba-Rusinov states in the unconventional superconductor FeTe0.55Se0.45
Authors: Chatzopoulos Damianos , Cho Doohee , Bastiaans Koen M. , Steffensen Gorm O. , Bouwmeester Damian , Akbari Alireza , Gu Genda , Paaske Jens , Andersen Brian M. , Allan Milan P.
Published: January 2021

By using scanning tunneling microscopy (STM) we find and characterize dispersive, energy-symmetric in-gap states in the iron-based superconductor FeTe0.55Se0.45, a material that exhibits signatures of topological superconductivity, and Majorana bound states at vortex cores or at impurity locations. We use a superconducting STM tip for enhanced energy resolution, which enables us to show that impurity states can be tuned through the Fermi level with varying tip-sample distance. We find that the impurity state is of the Yu-Shiba-Rusinov (YSR) type, and argue that the energy shift is caused by the low superfluid density in FeTe0.55Se0.45, which allows the electric field of the tip to slightly penetrate the sample. We model the newly introduced tip-gating scenario within the single-impurity Anderson model and find good agreement to the experimental data.
Tailoring of a visible-light-absorbing biaxial ferroelectric towards broadband self-driven photodetection
Authors: Han Shiguo , Li Maofan , Liu Yi , Guo Wuqian , Hong Mao-Chun , Sun Zhihua , Luo Junhua
Published: January 2021

In terms of strong light-polarization coupling, ferroelectric materials with bulk photovoltaic effects afford a promising avenue for optoelectronic devices. However, due to severe polarization deterioration caused by leakage current of photoexcited carriers, most of ferroelectrics are merely capable of absorbing 8–20% of visible-light spectra. Ferroelectrics with the narrow bandgap (<2.0 eV) are still scarce, hindering their practical applications. Here, we present a lead-iodide hybrid biaxial ferroelectric, (isopentylammonium)2(ethylammonium)2Pb3I10, which shows large spontaneous polarization (~5.2 μC/cm2) and a narrow direct bandgap (~1.80 eV). Particularly, the symmetry breaking of 4/mmmFmm2 species results in its biaxial attributes, which has four equivalent polar directions. Accordingly, exceptional in-plane photovoltaic effects are exploited along the crystallographic [001] and [010] axes directions inside the crystallographic bc-plane. The coupling between ferroelectricity and photovoltaic effects endows great possibility toward self-driven photodetection. This study sheds light on future optoelectronic device applications.
Engineering and elucidation of the lipoinitiation process in nonribosomal peptide biosynthesis
Authors: Zhong Lin , Diao Xiaotong , Zhang Na , Li Fengwei , Zhou Haibo , Chen Hanna , Bai Xianping , Ren Xintong , Zhang Youming , Wu Dalei , Bian Xiaoying
Published: January 2021

Nonribosomal peptide synthetases containing starter condensation domains direct the biosynthesis of nonribosomal lipopeptides, which generally exhibit wide bioactivities. The acyl chain has strong impacts on bioactivity and toxicity, but the lack of an in-depth understanding of starter condensation domain-mediated lipoinitiation limits the bioengineering of NRPSs to obtain novel derivatives with desired acyl chains. Here, we show that the acyl chains of the lipopeptides rhizomide, holrhizin, and glidobactin were modified by engineering the starter condensation domain, suggesting a workable approach to change the acyl chain. Based on the structure of the mutated starter condensation domain of rhizomide biosynthetic enzyme RzmA in complex with octanoyl-CoA and related point mutation experiments, we identify a set of residues responsible for the selectivity of substrate acyl chains and extend the acyl chains from acetyl to palmitoyl. Furthermore, we illustrate three possible conformational states of starter condensation domains during the reaction cycle of the lipoinitiation process. Our studies provide further insights into the mechanism of lipoinitiation and the engineering of nonribosomal peptide synthetases.
Millennial scale persistence of organic carbon bound to iron in Arctic marine sediments
Authors: Faust Johan C. , Tessin Allyson , Fisher Ben J. , Zindorf Mark , Papadaki Sonia , Hendry Katharine R. , Doyle Katherine A. , März Christian
Published: January 2021

Burial of organic material in marine sediments represents a dominant natural mechanism of long-term carbon sequestration globally, but critical aspects of this carbon sink remain unresolved. Investigation of surface sediments led to the proposition that on average 10-20% of sedimentary organic carbon is stabilised and physically protected against microbial degradation through binding to reactive metal (e.g. iron and manganese) oxides. Here we examine the long-term efficiency of this rusty carbon sink by analysing the chemical composition of sediments and pore waters from four locations in the Barents Sea. Our findings show that the carbon-iron coupling persists below the uppermost, oxygenated sediment layer over thousands of years. We further propose that authigenic coprecipitation is not the dominant factor of the carbon-iron bounding in these Arctic shelf sediments and that a substantial fraction of the organic carbon is already bound to reactive iron prior deposition on the seafloor.
A random-walk benchmark for single-electron circuits
Authors: Reifert David , Kokainis Martins , Ambainis Andris , Kashcheyevs Vyacheslavs , Ubbelohde Niels
Published: January 2021

Mesoscopic integrated circuits aim for precise control over elementary quantum systems. However, as fidelities improve, the increasingly rare errors and component crosstalk pose a challenge for validating error models and quantifying accuracy of circuit performance. Here we propose and implement a circuit-level benchmark that models fidelity as a random walk of an error syndrome, detected by an accumulating probe. Additionally, contributions of correlated noise, induced environmentally or by memory, are revealed as limits of achievable fidelity by statistical consistency analysis of the full distribution of error counts. Applying this methodology to a high-fidelity implementation of on-demand transfer of electrons in quantum dots we are able to utilize the high precision of charge counting to robustly estimate the error rate of the full circuit and its variability due to noise in the environment. As the clock frequency of the circuit is increased, the random walk reveals a memory effect. This benchmark contributes towards a rigorous metrology of quantum circuits.
Giant isotropic magneto-thermal conductivity of metallic spin liquid candidate Pr2Ir2O7 with quantum criticality
Authors: Ni J. M. , Huang Y. Y. , Cheng E. J. , Yu Y. J. , Pan B. L. , Li Q. , Xu L. M. , Tian Z. M. , Li S. Y.
Published: January 2021

Spin liquids are exotic states with no spontaneous symmetry breaking down to zero-temperature because of the highly entangled and fluctuating spins in frustrated systems. Exotic excitations like magnetic monopoles, visons, and photons may emerge from quantum spin ice states, a special kind of spin liquids in pyrochlore lattices. These materials usually are insulators, with an exception of the pyrochlore iridate Pr2Ir2O7, which was proposed as a metallic spin liquid located at a zero-field quantum critical point. Here we report the ultralow-temperature thermal conductivity measurements on Pr2Ir2O7. The Wiedemann–Franz law is verified at high fields and inferred at zero field, suggesting no breakdown of Landau quasiparticles at the quantum critical point, and the absence of mobile fermionic excitations. This result puts strong constraints on the description of the quantum criticality in Pr2Ir2O7. Unexpectedly, although the specific heats are anisotropic with respect to magnetic field directions, the thermal conductivities display the giant but isotropic response. This indicates that quadrupolar interactions and quantum fluctuations are important, which will help determine the true ground state of this material.
Interplay between chromosomal alterations and gene mutations shapes the evolutionary trajectory of clonal hematopoiesis
Authors: Gao Teng , Ptashkin Ryan , Bolton Kelly L. , Sirenko Maria , Fong Christopher , Spitzer Barbara , Menghrajani Kamal , Ossa Juan E. Arango , Zhou Yangyu , Bernard Elsa , Levine Max , Martinez Juan S. Medina , Zhang Yanming , Franch-Expósito Sebastià , Patel Minal , Braunstein Lior Z. , Kelly Daniel , Yabe Mariko , Benayed Ryma , Caltabellotta Nicole M. , Philip John , Paraiso Ederlinda , Mantha Simon , Solit David B. , Diaz Luis A. , Berger Michael F. , Klimek Virginia , Levine Ross L. , Zehir Ahmet , Devlin Sean M. , Papaemmanuil Elli
Published: January 2021

Stably acquired mutations in hematopoietic cells represent substrates of selection that may lead to clonal hematopoiesis (CH), a common state in cancer patients that is associated with a heightened risk of leukemia development. Owing to technical and sample size limitations, most CH studies have characterized gene mutations or mosaic chromosomal alterations (mCAs) individually. Here we leverage peripheral blood sequencing data from 32,442 cancer patients to jointly characterize gene mutations (n = 14,789) and mCAs (n = 383) in CH. Recurrent composite genotypes resembling known genetic interactions in leukemia genomes underlie 23% of all detected autosomal alterations, indicating that these selection mechanisms are operative early in clonal evolution. CH with composite genotypes defines a patient group at high risk of leukemia progression (3-year cumulative incidence 14.6%, CI: 7–22%). Multivariable analysis identifies mCA as an independent risk factor for leukemia development (HR = 14, 95% CI: 6–33, P < 0.001). Our results suggest that mCA should be considered in conjunction with gene mutations in the surveillance of patients at risk of hematologic neoplasms.
SCISSOR: a framework for identifying structural changes in RNA transcripts
Authors: Choi Hyo Young , Jo Heejoon , Zhao Xiaobei , Hoadley Katherine A. , Newman Scott , Holt Jeremiah , Hayward Michele C. , Love Michael I. , Marron J. S. , Hayes D. Neil
Published: January 2021

High-throughput sequencing protocols such as RNA-seq have made it possible to interrogate the sequence, structure and abundance of RNA transcripts at higher resolution than previous microarray and other molecular techniques. While many computational tools have been proposed for identifying mRNA variation through differential splicing/alternative exon usage, challenges in its analysis remain. Here, we propose a framework for unbiased and robust discovery of aberrant RNA transcript structures using short read sequencing data based on shape changes in an RNA-seq coverage profile. Shape changes in selecting sample outliers in RNA-seq, SCISSOR, is a series of procedures for transforming and normalizing base-level RNA sequencing coverage data in a transcript independent manner, followed by a statistical framework for its analysis (https://github.com/hyochoi/SCISSOR). The resulting high dimensional object is amenable to unsupervised screening of structural alterations across RNA-seq cohorts with nearly no assumption on the mutational mechanisms underlying abnormalities. This enables SCISSOR to independently recapture known variants such as splice site mutations in tumor suppressor genes as well as novel variants that are previously unrecognized or difficult to identify by any existing methods including recurrent alternate transcription start sites and recurrent complex deletions in 3′ UTRs.
Tumor-infiltrating mast cells are associated with resistance to anti-PD-1 therapy
Authors: Somasundaram Rajasekharan , Connelly Thomas , Choi Robin , Choi Hyeree , Samarkina Anastasia , Li Ling , Gregorio Elizabeth , Chen Yeqing , Thakur Rohit , Abdel-Mohsen Mohamed , Beqiri Marilda , Kiernan Meaghan , Perego Michela , Wang Fang , Xiao Min , Brafford Patricia , Yang Xue , Xu Xiaowei , Secreto Anthony , Danet-Desnoyers Gwenn , Traum Daniel , Kaestner Klaus H. , Huang Alexander C. , Hristova Denitsa , Wang Joshua , Fukunaga-Kalabis Mizuho , Krepler Clemens , Ping-Chen Fang , Zhou Xiangyang , Gutierrez Alexis , Rebecca Vito W. , Vonteddu Prashanthi , Dotiwala Farokh , Bala Shashi , Majumdar Sonali , Dweep Harsh , Wickramasinghe Jayamanna , Kossenkov Andrew V. , Reyes-Arbujas Jorge , Santiago Kenisha , Nguyen Tran , Griss Johannes , Keeney Frederick , Hayden James , Gavin Brian J. , Weiner David , Montaner Luis J. , Liu Qin , Peiffer Lukas , Becker Jürgen , Burton Elizabeth M. , Davies Michael A. , Tetzlaff Michael T. , Muthumani Kar , Wargo Jennifer A. , Gabrilovich Dmitry , Herlyn Meenhard
Published: January 2021

Anti-PD-1 therapy is used as a front-line treatment for many cancers, but mechanistic insight into this therapy resistance is still lacking. Here we generate a humanized (Hu)-mouse melanoma model by injecting fetal liver-derived CD34+ cells and implanting autologous thymus in immune-deficient NOD-scid IL2Rγnull (NSG) mice. Reconstituted Hu-mice are challenged with HLA-matched melanomas and treated with anti-PD-1, which results in restricted tumor growth but not complete regression. Tumor RNA-seq, multiplexed imaging and immunohistology staining show high expression of chemokines, as well as recruitment of FOXP3+ Treg and mast cells, in selective tumor regions. Reduced HLA-class I expression and CD8+/Granz B+ T cells homeostasis are observed in tumor regions where FOXP3+ Treg and mast cells co-localize, with such features associated with resistance to anti-PD-1 treatment. Combining anti-PD-1 with sunitinib or imatinib results in the depletion of mast cells and complete regression of tumors. Our results thus implicate mast cell depletion for improving the efficacy of anti-PD-1 therapy.
A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein
Authors: Kim Cheolmin , Ryu Dong-Kyun , Lee Jihun , Kim Young-Il , Seo Ji-Min , Kim Yeon-Gil , Jeong Jae-Hee , Kim Minsoo , Kim Jong-In , Kim Pankyeom , Bae Jin Soo , Shim Eun Yeong , Lee Min Seob , Kim Man Su , Noh Hanmi , Park Geun-Soo , Park Jae Sang , Son Dain , An Yongjin , Lee Jeong No , Kwon Ki-Sung , Lee Joo-Yeon , Lee Hansaem , Yang Jeong-Sun , Kim Kyung-Chang , Kim Sung Soon , Woo Hye-Min , Kim Jun-Won , Park Man-Seong , Yu Kwang-Min , Kim Se-Mi , Kim Eun-Ha , Park Su-Jin , Jeong Seong Tae , Yu Chi Ho , Song Youngjo , Gu Se Hun , Oh Hanseul , Koo Bon-Sang , Hong Jung Joo , Ryu Choong-Min , Park Wan Beom , Oh Myoung-don , Choi Young Ki , Lee Soo-Young
Published: January 2021

Vaccines and therapeutics are urgently needed for the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we screen human monoclonal antibodies (mAb) targeting the receptor binding domain (RBD) of the viral spike protein via antibody library constructed from peripheral blood mononuclear cells of a convalescent patient. The CT-P59 mAb potently neutralizes SARS-CoV-2 isolates including the D614G variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/RBD shows that CT-P59 blocks interaction regions of RBD for angiotensin converting enzyme 2 (ACE2) receptor with an orientation that is notably different from previously reported RBD-targeting mAbs. Furthermore, therapeutic effects of CT-P59 are evaluated in three animal models (ferret, hamster, and rhesus monkey), demonstrating a substantial reduction in viral titer along with alleviation of clinical symptoms. Therefore, CT-P59 may be a promising therapeutic candidate for COVID-19.
Granzyme B inhibition reduces disease severity in autoimmune blistering diseases
Authors: Hiroyasu Sho , Zeglinski Matthew R. , Zhao Hongyan , Pawluk Megan A. , Turner Christopher T. , Kasprick Anika , Tateishi Chiharu , Nishie Wataru , Burleigh Angela , Lennox Peter A. , Van Laeken Nancy , Carr Nick J. , Petersen Frank , Crawford Richard I. , Shimizu Hiroshi , Tsuruta Daisuke , Ludwig Ralf J. , Granville David J.
Published: January 2021

Pemphigoid diseases refer to a group of severe autoimmune skin blistering diseases characterized by subepidermal blistering and loss of dermal-epidermal adhesion induced by autoantibody and immune cell infiltrate at the dermal-epidermal junction and upper dermis. Here, we explore the role of the immune cell-secreted serine protease, granzyme B, in pemphigoid disease pathogenesis using three independent murine models. In all models, granzyme B knockout or topical pharmacological inhibition significantly reduces total blistering area compared to controls. In vivo and in vitro studies show that granzyme B contributes to blistering by degrading key anchoring proteins in the dermal-epidermal junction that are necessary for dermal-epidermal adhesion. Further, granzyme B mediates IL-8/macrophage inflammatory protein-2 secretion, lesional neutrophil infiltration, and lesional neutrophil elastase activity. Clinically, granzyme B is elevated and abundant in human pemphigoid disease blister fluids and lesional skin. Collectively, granzyme B is a potential therapeutic target in pemphigoid diseases.
H2AK121ub in Arabidopsis associates with a less accessible chromatin state at transcriptional regulation hotspots
Authors: Yin Xiaochang , Romero-Campero Francisco J. , de Los Reyes Pedro , Yan Peng , Yang Jing , Tian Guangmei , Yang XiaoZeng , Mo Xiaorong , Zhao Shuangshuang , Calonje Myriam , Zhou Yue
Published: January 2021

Although it is well established that the Polycomb Group (PcG) complexes maintain gene repression through the incorporation of H2AK121ub and H3K27me3, little is known about the effect of these modifications on chromatin accessibility, which is fundamental to understand PcG function. Here, by integrating chromatin accessibility, histone marks and expression analyses in different Arabidopsis PcG mutants, we show that PcG function regulates chromatin accessibility. We find that H2AK121ub is associated with a less accessible but still permissive chromatin at transcriptional regulation hotspots. Accessibility is further reduced by EMF1 acting in collaboration with PRC2 activity. Consequently, H2AK121ub/H3K27me3 marks are linked to inaccessible although responsive chromatin. In contrast, only-H3K27me3-marked chromatin is less responsive, indicating that H2AK121ub-marked hotspots are required for transcriptional responses. Nevertheless, despite the loss of PcG activities leads to increased chromatin accessibility, this is not necessarily accompanied by transcriptional activation, indicating that accessible chromatin is not always predictive of gene expression.