bluuebunny/crossref_metadata_2025_split huggingface dataset:
Type-I interferon signatures in SARS-CoV-2 infected Huh7 cells
Authors: Chen Xi , Saccon Elisa , Appelberg K. Sofia , Mikaeloff Flora , Rodriguez Jimmy Esneider , Vinhas Beatriz Sá , Frisan Teresa , Végvári Ákos , Mirazimi Ali , Neogi Ujjwal , Gupta Soham 
Published: May 2021

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes Coronavirus disease 2019 (COVID-19) has caused a global health emergency. A key feature of COVID-19 is dysregulated interferon-response. Type-I interferon (IFN-I) is one of the earliest antiviral innate immune responses following viral infection and plays a significant role in the pathogenesis of SARS-CoV-2. In this study, using a proteomics-based approach, we identified that SARS-CoV-2 infection induces delayed and dysregulated IFN-I signaling in Huh7 cells. We demonstrate that SARS-CoV-2 is able to inhibit RIG-I mediated IFN-β production. Our results also confirm the recent findings that IFN-I pretreatment is able to reduce the susceptibility of Huh7 cells to SARS-CoV-2, but not post-treatment. Moreover, senescent Huh7 cells, in spite of showing accentuated IFN-I response were more susceptible to SARS-CoV-2 infection, and the virus effectively inhibited IFIT1 in these cells. Finally, proteomic comparison between SARS-CoV-2, SARS-CoV, and MERS-CoV revealed a distinct differential regulatory signature of interferon-related proteins emphasizing that therapeutic strategies based on observations in SARS-CoV and MERS-CoV should be used with caution. Our findings provide a better understanding of SARS-CoV-2 regulation of cellular interferon response and a perspective on its use as a treatment. Investigation of different interferon-stimulated genes and their role in the inhibition of SARS-CoV-2 pathogenesis may direct novel antiviral strategies.
ROS induces NETosis by oxidizing DNA and initiating DNA repair
Authors: Azzouz Dhia , Khan Meraj A. , Palaniyar Nades 
Published: May 2021

AbstractReactive oxygen species (ROS) are essential for neutrophil extracellular trap (NET) formation or NETosis. Nevertheless, how ROS induces NETosis is unknown. Neutrophil activation induces excess ROS production and a meaningless genome-wide transcription to facilitate chromatin decondensation. Here we show that the induction of NADPH oxidase-dependent NETosis leads to extensive DNA damage, and the subsequent translocation of proliferating cell nuclear antigen (PCNA), a key DNA repair protein, stored in the cytoplasm into the nucleus. During the activation of NETosis (e.g., by phorbol myristate acetate,Escherichia coliLPS,Staphylococcus aureus(RN4220), orPseudomonas aeruginosa), preventing the DNA-repair-complex assembly leading to nick formation that decondenses chromatin causes the suppression of NETosis (e.g., by inhibitors to, or knockdown of, Apurinic endonuclease APE1, poly ADP ribose polymerase PARP, and DNA ligase). The remaining repair steps involving polymerase activity and PCNA interactions with DNA polymerases β/δ do not suppress agonist-induced NETosis. Therefore, excess ROS produced during neutrophil activation induces NETosis by inducing extensive DNA damage (e.g., oxidising guanine to 8-oxoguanine), and the subsequent DNA repair pathway, leading to chromatin decondensation.
Spatio-temporal landscape of mouse epididymal cells and specific mitochondria-rich segments defined by large-scale single-cell RNA-seq
Authors: Shi Jianwu , Fok Kin Lam , Dai Pengyuan , Qiao Feng , Zhang Mengya , Liu Huage , Sang Mengmeng , Ye Mei , Liu Yang , Zhou Yiwen , Wang Chengniu , Sun Fei , Xie Gangcai , Chen Hao 
Published: May 2021

AbstractSpermatozoa acquire their fertilizing ability and forward motility during epididymal transit, suggesting the importance of the epididymis. Although the cell atlas of the epididymis was reported recently, the heterogeneity of the cells and the gene expression profile in the epididymal tube are still largely unknown. Considering single-cell RNA sequencing results, we thoroughly studied the cell composition, spatio-temporal differences in differentially expressed genes (DEGs) in epididymal segments and mitochondria throughout the epididymis with sufficient cell numbers. In total, 40,623 cells were detected and further clustered into 8 identified cell populations. Focused analyses revealed the subpopulations of principal cells, basal cells, clear/narrow cells, and halo/T cells. Notably, two subtypes of principal cells, the Prc7 and Prc8 subpopulations were enriched as stereocilia-like cells according to GO analysis. Further analysis demonstrated the spatially specific pattern of the DEGs in each cell cluster. Unexpectedly, the abundance of mitochondria and mitochondrial transcription (MT) was found to be higher in the corpus and cauda epididymis than in the caput epididymis by scRNA-seq, immunostaining, and qPCR validation. In addition, the spatio-temporal profile of the DEGs from the P42 and P56 epididymis, including transiting spermatozoa, was depicted. Overall, our study presented the single-cell transcriptome atlas of the mouse epididymis and revealed the novel distribution pattern of mitochondria and key genes that may be linked to sperm functionalities in the first wave and subsequent wave of sperm, providing a roadmap to be emulated in efforts to achieve sperm maturation regulation in the epididymis.
Mycobacterium tuberculosis precursor rRNA as a measure of treatment-shortening activity of drugs and regimens
Authors: Walter Nicholas D. , Born Sarah E. M. , Robertson Gregory T. , Reichlen Matthew , Dide-Agossou Christian , Ektnitphong Victoria A. , Rossmassler Karen , Ramey Michelle E. , Bauman Allison A. , Ozols Victor , Bearrows Shelby C. , Schoolnik Gary , Dolganov Gregory , Garcia Benjamin , Musisi Emmanuel , Worodria William , Huang Laurence , Davis J. Lucian , Nguyen Nhung V. , Nguyen Hung V. , Nguyen Anh T. V. , Phan Ha , Wilusz Carol , Podell Brendan K. , Sanoussi N’ Dira , de Jong Bouke C. , Merle Corinne S. , Affolabi Dissou , McIlleron Helen , Garcia-Cremades Maria , Maidji Ekaterina , Eshun-Wilson Franceen , Aguilar-Rodriguez Brandon , Karthikeyan Dhuvarakesh , Mdluli Khisimuzi , Bansbach Cathy , Lenaerts Anne J. , Savic Radojka M. , Nahid Payam , Vásquez Joshua J. , Voskuil Martin I. 
Published: May 2021

AbstractThere is urgent need for new drug regimens that more rapidly cure tuberculosis (TB). Existing TB drugs and regimens vary in treatment-shortening activity, but the molecular basis of these differences is unclear, and no existing assay directly quantifies the ability of a drug or regimen to shorten treatment. Here, we show that drugs historically classified as sterilizing and non-sterilizing have distinct impacts on a fundamental aspect of Mycobacterium tuberculosis physiology: ribosomal RNA (rRNA) synthesis. In culture, in mice, and in human studies, measurement of precursor rRNA reveals that sterilizing drugs and highly effective drug regimens profoundly suppress M. tuberculosis rRNA synthesis, whereas non-sterilizing drugs and weaker regimens do not. The rRNA synthesis ratio provides a readout of drug effect that is orthogonal to traditional measures of bacterial burden. We propose that this metric of drug activity may accelerate the development of shorter TB regimens.
The effect of generic market entry on antibiotic prescriptions in the United States
Authors: Kållberg Cecilia , Hudson Jemma , Salvesen Blix Hege , Årdal Christine , Klein Eili , Lindbæk Morten , Outterson Kevin , Røttingen John-Arne , Laxminarayan Ramanan 
Published: May 2021

AbstractWhen patented, brand-name antibiotics lose market exclusivity, generics typically enter the market at lower prices, which may increase consumption of the drug. To examine the effect of generic market entry on antibiotic consumption in the United States, we conducted an interrupted time series analysis of the change in the number of prescriptions per month for antibiotics for which at least one generic entered the US market between 2000 and 2012. Data were acquired from the IQVIA Xponent database. Thirteen antibiotics were analyzed. Here, we show that one year after generic entry, the number of prescriptions increased for five antibiotics (5 to 406%)—aztreonam, cefpodoxime, ciprofloxacin, levofloxacin, ofloxacin—and decreased for one drug: cefdinir. These changes were sustained two years after. Cefprozil, cefuroxime axetil and clarithromycin had significant increases in trend, but no significant level changes. No consistent pattern for antibiotic use following generic entry in the United States was observed.
A well-timed shift from local to global agreements accelerates climate change mitigation
Authors: Karatayev Vadim A. , Vasconcelos Vítor V. , Lafuite Anne-Sophie , Levin Simon A. , Bauch Chris T. , Anand Madhur 
Published: May 2021

AbstractRecent attempts at cooperating on climate change mitigation highlight the limited efficacy of large-scale negotiations, when commitment to mitigation is costly and initially rare. Deepening existing voluntary mitigation pledges could require more stringent, legally-binding agreements that currently remain untenable at the global scale. Building-blocks approaches promise greater success by localizing agreements to regions or few-nation summits, but risk slowing mitigation adoption globally. Here, we show that a well-timed policy shift from local to global legally-binding agreements can dramatically accelerate mitigation compared to using only local, only global, or both agreement types simultaneously. This highlights the scale-specific roles of mitigation incentives: local agreements promote and sustain mitigation commitments in early-adopting groups, after which global agreements rapidly draw in late-adopting groups. We conclude that focusing negotiations on local legally-binding agreements and, as these become common, a renewed pursuit of stringent, legally-binding world-wide agreements could best overcome many current challenges facing climate mitigation.
Low coordination number copper catalysts for electrochemical CO2 methanation in a membrane electrode assembly
Authors: Xu Yi , Li Fengwang , Xu Aoni , Edwards Jonathan P. , Hung Sung-Fu , Gabardo Christine M. , O’Brien Colin P. , Liu Shijie , Wang Xue , Li Yuhang , Wicks Joshua , Miao Rui Kai , Liu Yuan , Li Jun , Huang Jianan Erick , Abed Jehad , Wang Yuhang , Sargent Edward H. , Sinton David 
Published: May 2021

AbstractThe electrochemical conversion of CO2 to methane provides a means to store intermittent renewable electricity in the form of a carbon-neutral hydrocarbon fuel that benefits from an established global distribution network. The stability and selectivity of reported approaches reside below technoeconomic-related requirements. Membrane electrode assembly-based reactors offer a known path to stability; however, highly alkaline conditions on the cathode favour C-C coupling and multi-carbon products. In computational studies herein, we find that copper in a low coordination number favours methane even under highly alkaline conditions. Experimentally, we develop a carbon nanoparticle moderator strategy that confines a copper-complex catalyst when employed in a membrane electrode assembly. In-situ XAS measurements confirm that increased carbon nanoparticle loadings can reduce the metallic copper coordination number. At a copper coordination number of 4.2 we demonstrate a CO2-to-methane selectivity of 62%, a methane partial current density of 136 mA cm−2, and > 110 hours of stable operation.
Spectral bias and task-model alignment explain generalization in kernel regression and infinitely wide neural networks
Authors: Canatar Abdulkadir , Bordelon Blake , Pehlevan Cengiz 
Published: May 2021

AbstractA theoretical understanding of generalization remains an open problem for many machine learning models, including deep networks where overparameterization leads to better performance, contradicting the conventional wisdom from classical statistics. Here, we investigate generalization error for kernel regression, which, besides being a popular machine learning method, also describes certain infinitely overparameterized neural networks. We use techniques from statistical mechanics to derive an analytical expression for generalization error applicable to any kernel and data distribution. We present applications of our theory to real and synthetic datasets, and for many kernels including those that arise from training deep networks in the infinite-width limit. We elucidate an inductive bias of kernel regression to explain data with simple functions, characterize whether a kernel is compatible with a learning task, and show that more data may impair generalization when noisy or not expressible by the kernel, leading to non-monotonic learning curves with possibly many peaks.
Superconductor-insulator transition in space charge doped one unit cell Bi2.1Sr1.9CaCu2O8+x
Authors: Wang Fang , Biscaras Johan , Erb Andreas , Shukla Abhay 
Published: May 2021

AbstractThe superconductor-insulator transition in two dimensions is a prototype continuous quantum phase transition at absolute zero, driven by a parameter other than temperature. Here we reveal this transition in one unit-cell Bi2.1Sr1.9CaCu2O8+x by space charge doping, a field effect electrostatic doping technique. We determine the related critical parameters and develop a reliable way to estimate doping in the nonsuperconducting region, a crucial and central problem in these materials. Finite-size scaling analysis yields a critical doping of 0.057 holes/Cu, a critical resistance of ~6.85 kΩ and a scaling exponent product νz ~ 1.57. These results, together with earlier work in other materials, provide a coherent picture of the superconductor-insulator transition and its bosonic nature in the underdoped regime of emerging superconductivity in high critical temperature superconductors.
Biomimetic high performance artificial muscle built on sacrificial coordination network and mechanical training process
Authors: Tu Zhikai , Liu Weifeng , Wang Jin , Qiu Xueqing , Huang Jinhao , Li Jinxing , Lou Hongming 
Published: May 2021

AbstractArtificial muscle materials promise incredible applications in actuators, robotics and medical apparatus, yet the ability to mimic the full characteristics of skeletal muscles into synthetic materials remains a huge challenge. Herein, inspired by the dynamic sacrificial bonds in biomaterials and the self-strengthening of skeletal muscles by physical exercise, high performance artificial muscle material is prepared by rearrangement of sacrificial coordination bonds in the polyolefin elastomer via a repetitive mechanical training process. Biomass lignin is incorporated as a green reinforcer for the construction of interfacial coordination bonds. The prepared artificial muscle material exhibits high actuation strain (>40%), high actuation stress (1.5 MPa) which can lift more than 10,000 times its own weight with 30% strain, characteristics of excellent self-strengthening by mechanical training, strain-adaptive stiffening, and heat/electric programmable actuation performance. In this work, we show a facile strategy for the fabrication of intelligent materials using easily available raw materials.
Guiding functions of the C-terminal domain of topoisomerase IIα advance mitotic chromosome assembly
Authors: Shintomi Keishi , Hirano Tatsuya 
Published: May 2021

AbstractTopoisomerase II (topo II) is one of the six proteins essential for mitotic chromatid reconstitution in vitro. It is not fully understood, however, mechanistically how this enzyme regulates this process. In an attempt to further refine the reconstitution assay, we have found that chromosomal binding of Xenopus laevis topo IIα is sensitive to buffer conditions and depends on its C-terminal domain (CTD). Enzymological assays using circular DNA substrates supports the idea that topo IIα first resolves inter-chromatid entanglements to drive individualization and then generates intra-chromatid entanglements to promote thickening. Importantly, only the latter process requires the CTD. By using frog egg extracts, we also show that the CTD contributes to proper formation of nucleosome-depleted chromatids by competing with a linker histone for non-nucleosomal DNA. Our results demonstrate that topo IIα utilizes its CTD to deliver the enzymatic core to crowded environments created during mitotic chromatid assembly, thereby fine-tuning this process.
CD8+ T cell landscape in Indigenous and non-Indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph
Authors: Hensen Luca , Illing Patricia T. , Bridie Clemens E. , Nguyen Thi H. O. , Koutsakos Marios , van de Sandt Carolien E. , Mifsud Nicole A. , Nguyen Andrea T. , Szeto Christopher , Chua Brendon Y. , Halim Hanim , Rizzetto Simone , Luciani Fabio , Loh Liyen , Grant Emma J. , Saunders Phillipa M. , Brooks Andrew G. , Rockman Steve , Kotsimbos Tom C. , Cheng Allen C. , Richards Michael , Westall Glen P. , Wakim Linda M. , Loudovaris Thomas , Mannering Stuart I. , Elliott Michael , Tangye Stuart G. , Jackson David C. , Flanagan Katie L. , Rossjohn Jamie , Gras Stephanie , Davies Jane , Miller Adrian , Tong Steven Y. C. , Purcell Anthony W. , Kedzierska Katherine 
Published: May 2021

AbstractIndigenous people worldwide are at high risk of developing severe influenza disease. HLA-A*24:02 allele, highly prevalent in Indigenous populations, is associated with influenza-induced mortality, although the basis for this association is unclear. Here, we define CD8+ T-cell immune landscapes against influenza A (IAV) and B (IBV) viruses in HLA-A*24:02-expressing Indigenous and non-Indigenous individuals, human tissues, influenza-infected patients and HLA-A*24:02-transgenic mice. We identify immunodominant protective CD8+ T-cell epitopes, one towards IAV and six towards IBV, with A24/PB2550–558-specific CD8+ T cells being cross-reactive between IAV and IBV. Memory CD8+ T cells towards these specificities are present in blood (CD27+CD45RA− phenotype) and tissues (CD103+CD69+ phenotype) of healthy individuals, and effector CD27−CD45RA−PD-1+CD38+CD8+ T cells in IAV/IBV patients. Our data show influenza-specific CD8+ T-cell responses in Indigenous Australians, and advocate for T-cell-mediated vaccines that target and boost the breadth of IAV/IBV-specific CD8+ T cells to protect high-risk HLA-A*24:02-expressing Indigenous and non-Indigenous populations from severe influenza disease.
PLGA-particle vaccine carrying TLR3/RIG-I ligand Riboxxim synergizes with immune checkpoint blockade for effective anti-cancer immunotherapy
Authors: Koerner Julia , Horvath Dennis , Herrmann Valerie L. , MacKerracher Anna , Gander Bruno , Yagita Hideo , Rohayem Jacques , Groettrup Marcus 
Published: May 2021

AbstractWith emerging supremacy, cancer immunotherapy has evolved as a promising therapeutic modality compared to conventional antitumor therapies. Cancer immunotherapy composed of biodegradable poly(lactic-co-glycolic acid) (PLGA) particles containing antigens and toll-like receptor ligands induces vigorous antitumor immune responses in vivo. Here, we demonstrate the supreme adjuvant effect of the recently developed and pharmaceutically defined double-stranded (ds)RNA adjuvant Riboxxim especially when incorporated into PLGA particles. Encapsulation of Riboxxim together with antigens potently activates murine and human dendritic cells, and elevated tumor-specific CD8+ T cell responses are superior to those obtained using classical dsRNA analogues. This PLGA particle vaccine affords primary tumor growth retardation, prevention of metastases, and prolonged survival in preclinical tumor models. Its advantageous therapeutic potency was further enhanced by immune checkpoint blockade that resulted in reinvigoration of cytotoxic T lymphocyte responses and tumor ablation. Thus, combining immune checkpoint blockade with immunotherapy based on Riboxxim-bearing PLGA particles strongly increases its efficacy.
Localized corrosion induced surface modifications of Al-Cu-Li alloy studied by ToF-SIMS 3D imaging
Authors: Li Meicheng , Seyeux Antoine , Wiame Frédéric , Marcus Philippe , Światowska Jolanta 
Published: May 2021

AbstractThree-dimensional (3D) time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging is a promising tool in the analysis of surface modifications of alloy matrix and intermetallic particles induced by localized corrosion due to its good spatial resolution and very high sensitivity to chemical identification especially involving light mass elements like Li. In this paper, ToF-SIMS 3D chemical mapping combined with scanning electron microscopy was performed to study the localized corrosion of Al-Cu-Li alloy (AA2050-T8) in a region around an Al-Cu-Fe-Mn intermetallic particles (IMPs) in 0. 1 M NaCl solution. Initiation of corrosion was locally observed on the IMPs and between IMPs and matrix substrate. Moreover, a modified oxide/hydroxide layer was observed over IMPs compared to the matrix. This new corrosion layer was enriched with chlorides and Cu hydroxides. ToF-SIMS 3D imaging revealed that Li was present over the alloy matrix, while no Li was present over the IMPs in regions where localized corrosion occurred.
Experimental realization of phase-controlled dynamics with hybrid digital–analog approach
Authors: Tao Ziyu , Zhang Libo , Li Xiaole , Niu Jingjing , Luo Kai , Yi Kangyuan , Zhou Yuxuan , Jia Hao , Zhang Xu , Liu Song , Yan Tongxing , Chen Yuanzhen , Yu Dapeng 
Published: May 2021

AbstractQuantum simulation can be implemented in pure digital or analog ways, each with their pros and cons. By taking advantage of the universality of a digital route and the efficiency of analog simulation, hybrid digital–analog approaches can enrich the possibilities for quantum simulation. We use a hybrid approach to experimentally perform a quantum simulation of phase-controlled dynamics resulting from a closed-contour interaction (CCI) within certain multi-level systems in superconducting quantum circuits. Due to symmetry constraints, such systems cannot host an inherent CCI. Nevertheless, by assembling analog modules corresponding to their natural evolutions and specially designed digital modules constructed from standard quantum logic gates, we can bypass such constraints and realize an effective CCI in these systems. Based on this realization, we demonstrate a variety of related and interesting phenomena, including phase-controlled chiral dynamics, separation of chiral enantiomers, and a mechanism to generate entangled states based on CCI.