bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell immune profiling reveals distinct immune response in asymptomatic COVID-19 patients
Authors: Zhao Xiang-Na , You Yue , Cui Xiao-Ming , Gao Hui-Xia , Wang Guo-Lin , Zhang Sheng-Bo , Yao Lin , Duan Li-Jun , Zhu Ka-Li , Wang Yu-Ling , Li Li , Lu Jian-Hua , Wang Hai-Bin , Fan Jing-Fang , Zheng Huan-Wei , Dai Er-Hei , Tian Lu-Yi , Ma Mai-Juan 
Published: September 2021

AbstractWhile some individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present mild-to-severe disease, many SARS-CoV-2-infected individuals are asymptomatic. We sought to identify the distinction of immune response between asymptomatic and moderate patients. We performed single-cell transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing in 37 longitudinal collected peripheral blood mononuclear cell samples from asymptomatic, moderate, and severe patients with healthy controls. Asymptomatic patients displayed increased CD56briCD16−natural killer (NK) cells and upregulation of interferon-gamma in effector CD4+and CD8+T cells and NK cells. They showed more robust TCR clonal expansion, especially in effector CD4+T cells, but lack strong BCR clonal expansion compared to moderate patients. Moreover, asymptomatic patients have lower interferon-stimulated genes (ISGs) expression in general but large interpatient variability, whereas moderate patients showed various magnitude and temporal dynamics of the ISGs expression across multiple cell populations but lower than a patient with severe disease. Our data provide evidence of different immune signatures to SARS-CoV-2 in asymptomatic infections.
Electrophysiological biomarkers of behavioral dimensions from cross-species paradigms
Authors: Cavanagh James F. , Gregg David , Light Gregory A. , Olguin Sarah L. , Sharp Richard F. , Bismark Andrew W. , Bhakta Savita G. , Swerdlow Neal R. , Brigman Jonathan L. , Young Jared W. 
Published: September 2021

AbstractThere has been a fundamental failure to translate preclinically supported research into clinically efficacious treatments for psychiatric disorders. One of the greatest impediments toward improving this species gap has been the difficulty of identifying translatable neurophysiological signals that are related to specific behavioral constructs. Here, we present evidence from three paradigms that were completed by humans and mice using analogous procedures, with each task eliciting candidate a priori defined electrophysiological signals underlying effortful motivation, reinforcement learning, and cognitive control. The effortful motivation was assessed using a progressive ratio breakpoint task, yielding a similar decrease in alpha-band activity over time in both species. Reinforcement learning was assessed via feedback in a probabilistic learning task with delta power significantly modulated by reward surprise in both species. Additionally, cognitive control was assessed in the five-choice continuous performance task, yielding response-locked theta power seen across species, and modulated by difficulty in humans. Together, these successes, and also the teachings from these failures, provide a roadmap towards the use of electrophysiology as a method for translating findings from the preclinical assays to the clinical settings.
PRMT5 regulates cell pyroptosis by silencing CASP1 in multiple myeloma
Authors: Xia Tian , Liu Ming , Zhao Quan , Ouyang Jian , Xu Peipei , Chen Bing 
Published: September 2021

AbstractProtein arginine methyltransferase 5 (PRMT5), a histone methyltransferase responsible for the symmetric dimethylation of histone H4 on Arg 3 (H4R3me2s), is an enzyme that participates in tumor cell progression in a variety of hematological malignancies. However, the biological functions of PRMT5 in multiple myeloma (MM) and the underlying molecular mechanisms remain unclear. In this study, we conducted a bioinformatics analysis and found that PRMT5 expression was significantly upregulated in MM. In vitro and in vivo phenotypic experiments revealed that knockdown of PRMT5 expression enhanced cell pyroptosis in MM. Moreover, we found that CASP1 expression was negatively correlated with PRMT5 expression, and repressing PRMT5 expression rescued both the phenotype and expression markers (N-GSDMD, IL-1b, and IL-18). Inhibition of PRMT5 activity increased CASP1 expression and promoted MM cell pyroptosis. Finally, high expression of PRMT5 or low expression of CASP1 was correlated with poor overall survival in MM. Collectively, our results provide a mechanism by which PRMT5 regulates cell pyroptosis by silencing CASP1 in MM.
Bicc1 and Dicer regulate left-right patterning through post-transcriptional control of the Nodal inhibitor Dand5
Authors: Maerker Markus , Getwan Maike , Dowdle Megan E. , McSheene Jason C. , Gonzalez Vanessa , Pelliccia José L. , Hamilton Danielle S. , Yartseva Valeria , Vejnar Charles , Tingler Melanie , Minegishi Katsura , Vick Philipp , Giraldez Antonio J. , Hamada Hiroshi , Burdine Rebecca D. , Sheets Michael D. , Blum Martin , Schweickert Axel 
Published: September 2021

AbstractRotating cilia at the vertebrate left-right organizer (LRO) generate an asymmetric leftward flow, which is sensed by cells at the left LRO margin. Ciliary activity of the calcium channel Pkd2 is crucial for flow sensing. How this flow signal is further processed and relayed to the laterality-determining Nodal cascade in the left lateral plate mesoderm (LPM) is largely unknown. We previously showed that flow down-regulates mRNA expression of the Nodal inhibitor Dand5 in left sensory cells. De-repression of the co-expressed Nodal, complexed with the TGFß growth factor Gdf3, drives LPM Nodal cascade induction. Here, we show that post-transcriptional repression of dand5 is a central process in symmetry breaking of Xenopus, zebrafish and mouse. The RNA binding protein Bicc1 was identified as a post-transcriptional regulator of dand5 and gdf3 via their 3′-UTRs. Two distinct Bicc1 functions on dand5 mRNA were observed at pre- and post-flow stages, affecting mRNA stability or flow induced translational inhibition, respectively. To repress dand5, Bicc1 co-operates with Dicer1, placing both proteins in the process of flow sensing. Intriguingly, Bicc1 mediated translational repression of a dand5 3′-UTR mRNA reporter was responsive to pkd2, suggesting that a flow induced Pkd2 signal triggers Bicc1 mediated dand5 inhibition during symmetry breakage.
A human liver cell-based system modeling a clinical prognostic liver signature for therapeutic discovery
Authors: Crouchet Emilie , Bandiera Simonetta , Fujiwara Naoto , Li Shen , El Saghire Hussein , Fernández-Vaquero Mirian , Riedl Tobias , Sun Xiaochen , Hirschfield Hadassa , Jühling Frank , Zhu Shijia , Roehlen Natascha , Ponsolles Clara , Heydmann Laura , Saviano Antonio , Qian Tongqi , Venkatesh Anu , Lupberger Joachim , Verrier Eloi R. , Sojoodi Mozhdeh , Oudot Marine A. , Duong François H. T. , Masia Ricard , Wei Lan , Thumann Christine , Durand Sarah C. , González-Motos Victor , Heide Danijela , Hetzer Jenny , Nakagawa Shigeki , Ono Atsushi , Song Won-Min , Higashi Takaaki , Sanchez Roberto , Kim Rosa S. , Bian C. Billie , Kiani Karun , Croonenborghs Tom , Subramanian Aravind , Chung Raymond T. , Straub Beate K. , Schuppan Detlef , Ankavay Maliki , Cocquerel Laurence , Schaeffer Evelyne , Goossens Nicolas , Koh Anna P. , Mahajan Milind , Nair Venugopalan D. , Gunasekaran Ganesh , Schwartz Myron E. , Bardeesy Nabeel , Shalek Alex K. , Rozenblatt-Rosen Orit , Regev Aviv , Felli Emanuele , Pessaux Patrick , Tanabe Kenneth K. , Heikenwälder Mathias , Schuster Catherine , Pochet Nathalie , Zeisel Mirjam B. , Fuchs Bryan C. , Hoshida Yujin , Baumert Thomas F. 
Published: September 2021

AbstractChronic liver disease and hepatocellular carcinoma (HCC) are life-threatening diseases with limited treatment options. The lack of clinically relevant/tractable experimental models hampers therapeutic discovery. Here, we develop a simple and robust human liver cell-based system modeling a clinical prognostic liver signature (PLS) predicting long-term liver disease progression toward HCC. Using the PLS as a readout, followed by validation in nonalcoholic steatohepatitis/fibrosis/HCC animal models and patient-derived liver spheroids, we identify nizatidine, a histamine receptor H2 (HRH2) blocker, for treatment of advanced liver disease and HCC chemoprevention. Moreover, perturbation studies combined with single cell RNA-Seq analyses of patient liver tissues uncover hepatocytes and HRH2+, CLEC5Ahigh, MARCOlow liver macrophages as potential nizatidine targets. The PLS model combined with single cell RNA-Seq of patient tissues enables discovery of urgently needed targets and therapeutics for treatment of advanced liver disease and cancer prevention.
Diel cycle of sea spray aerosol concentration
Authors: Flores J. Michel , Bourdin Guillaume , Kostinski Alexander B. , Altaratz Orit , Dagan Guy , Lombard Fabien , Haëntjens Nils , Boss Emmanuel , Sullivan Matthew B. , Gorsky Gabriel , Lang-Yona Naama , Trainic Miri , Romac Sarah , Voolstra Christian R. , Rudich Yinon , Vardi Assaf , Koren Ilan 
Published: September 2021

AbstractSea spray aerosol (SSA) formation have a major role in the climate system, but measurements at a global-scale of this micro-scale process are highly challenging. We measured high-resolution temporal patterns of SSA number concentration over the Atlantic Ocean, Caribbean Sea, and the Pacific Ocean covering over 42,000 km. We discovered a ubiquitous 24-hour rhythm to the SSA number concentration, with concentrations increasing after sunrise, remaining higher during the day, and returning to predawn values after sunset. The presence of dominating continental aerosol transport can mask the SSA cycle. We did not find significant links between the diel cycle of SSA number concentration and diel variations of surface winds, atmospheric physical properties, radiation, pollution, nor oceanic physical properties. However, the daily mean sea surface temperature positively correlated with the magnitude of the day-to-nighttime increase in SSA concentration. Parallel diel patterns in particle sizes were also detected in near-surface waters attributed to variations in the size of particles smaller than ~1 µm. These variations may point to microbial day-to-night modulation of bubble-bursting dynamics as a possible cause of the SSA cycle.
Pericyte-derived fibrotic scarring is conserved across diverse central nervous system lesions
Authors: Dias David O. , Kalkitsas Jannis , Kelahmetoglu Yildiz , Estrada Cynthia P. , Tatarishvili Jemal , Holl Daniel , Jansson Linda , Banitalebi Shervin , Amiry-Moghaddam Mahmood , Ernst Aurélie , Huttner Hagen B. , Kokaia Zaal , Lindvall Olle , Brundin Lou , Frisén Jonas , Göritz Christian 
Published: September 2021

AbstractFibrotic scar tissue limits central nervous system regeneration in adult mammals. The extent of fibrotic tissue generation and distribution of stromal cells across different lesions in the brain and spinal cord has not been systematically investigated in mice and humans. Furthermore, it is unknown whether scar-forming stromal cells have the same origin throughout the central nervous system and in different types of lesions. In the current study, we compared fibrotic scarring in human pathological tissue and corresponding mouse models of penetrating and non-penetrating spinal cord injury, traumatic brain injury, ischemic stroke, multiple sclerosis and glioblastoma. We show that the extent and distribution of stromal cells are specific to the type of lesion and, in most cases, similar between mice and humans. Employing in vivo lineage tracing, we report that in all mouse models that develop fibrotic tissue, the primary source of scar-forming fibroblasts is a discrete subset of perivascular cells, termed type A pericytes. Perivascular cells with a type A pericyte marker profile also exist in the human brain and spinal cord. We uncover type A pericyte-derived fibrosis as a conserved mechanism that may be explored as a therapeutic target to improve recovery after central nervous system lesions.
Activation mechanism of human soluble guanylate cyclase by stimulators and activators
Authors: Liu Rui , Kang Yunlu , Chen Lei 
Published: September 2021

AbstractSoluble guanylate cyclase (sGC) is the receptor for nitric oxide (NO) in human. It is an important validated drug target for cardiovascular diseases. sGC can be pharmacologically activated by stimulators and activators. However, the detailed structural mechanisms, through which sGC is recognized and positively modulated by these drugs at high spacial resolution, are poorly understood. Here, we present cryo-electron microscopy structures of human sGC in complex with NO and sGC stimulators, YC-1 and riociguat, and also in complex with the activator cinaciguat. These structures uncover the molecular details of how stimulators interact with residues from both β H-NOX and CC domains, to stabilize sGC in the extended active conformation. In contrast, cinaciguat occupies the haem pocket in the β H-NOX domain and sGC shows both inactive and active conformations. These structures suggest a converged mechanism of sGC activation by pharmacological compounds.
The cichlid oral and pharyngeal jaws are evolutionarily and genetically coupled
Authors: Conith Andrew J. , Albertson R. Craig 
Published: September 2021

AbstractEvolutionary constraints may significantly bias phenotypic change, while “breaking” from such constraints can lead to expanded ecological opportunity. Ray-finned fishes have broken functional constraints by developing two jaws (oral-pharyngeal), decoupling prey capture (oral jaw) from processing (pharyngeal jaw). It is hypothesized that the oral and pharyngeal jaws represent independent evolutionary modules and this facilitated diversification in feeding architectures. Here we test this hypothesis in African cichlids. Contrary to our expectation, we find integration between jaws at multiple evolutionary levels. Next, we document integration at the genetic level, and identify a candidate gene, smad7, within a pleiotropic locus for oral and pharyngeal jaw shape that exhibits correlated expression between the two tissues. Collectively, our data show that African cichlid evolutionary success has occurred within the context of a coupled jaw system, an attribute that may be driving adaptive evolution in this iconic group by facilitating rapid shifts between foraging habitats, providing an advantage in a stochastic environment such as the East African Rift-Valley.
Aerodynamics-assisted, efficient and scalable kirigami fog collectors
Authors: Li Jing , Ran Ranjiangshang , Wang Haihuan , Wang Yuchen , Chen You , Niu Shichao , Arratia Paulo E. , Yang Shu 
Published: September 2021

AbstractTo address the global water shortage crisis, one of the promising solutions is to collect freshwater from the environmental resources such as fog. However, the efficiency of conventional fog collectors remains low due to the viscous drag of fog-laden wind deflected around the collecting surface. Here, we show that the three-dimensional and centimetric kirigami structures can control the wind flow, forming quasi-stable counter-rotating vortices. The vortices regulate the trajectories of incoming fog clusters and eject extensive droplets to the substrate. As the characteristic structural length is increased to the size of vortices, we greatly reduce the dependence of fog collection on the structural delicacy. Together with gravity-directed gathering by the folds, the kirigami fog collector yields a collection efficiency of 16.1% at a low wind speed of 0.8 m/s and is robust against surface characteristics. The collection efficiency is maintained even on a 1 m2 collector in an outdoor setting.
Automated bone mineral density prediction and fracture risk assessment using plain radiographs via deep learning
Authors: Hsieh Chen-I , Zheng Kang , Lin Chihung , Mei Ling , Lu Le , Li Weijian , Chen Fang-Ping , Wang Yirui , Zhou Xiaoyun , Wang Fakai , Xie Guotong , Xiao Jing , Miao Shun , Kuo Chang-Fu 
Published: September 2021

AbstractDual-energy X-ray absorptiometry (DXA) is underutilized to measure bone mineral density (BMD) and evaluate fracture risk. We present an automated tool to identify fractures, predict BMD, and evaluate fracture risk using plain radiographs. The tool performance is evaluated on 5164 and 18175 patients with pelvis/lumbar spine radiographs and Hologic DXA. The model is well calibrated with minimal bias in the hip (slope = 0.982, calibration-in-the-large = −0.003) and the lumbar spine BMD (slope = 0.978, calibration-in-the-large = 0.003). The area under the precision-recall curve and accuracy are 0.89 and 91.7% for hip osteoporosis, 0.89 and 86.2% for spine osteoporosis, 0.83 and 95.0% for high 10-year major fracture risk, and 0.96 and 90.0% for high hip fracture risk. The tool classifies 5206 (84.8%) patients with 95% positive or negative predictive value for osteoporosis, compared to 3008 DXA conducted at the same study period. This automated tool may help identify high-risk patients for osteoporosis.
Spatially and optically tailored 3D printing for highly miniaturized and integrated microfluidics
Authors: Sanchez Noriega Jose L. , Chartrand Nicholas A. , Valdoz Jonard Corpuz , Cribbs Collin G. , Jacobs Dallin A. , Poulson Daniel , Viglione Matthew S. , Woolley Adam T. , Van Ry Pam M. , Christensen Kenneth A. , Nordin Gregory P. 
Published: September 2021

AbstractTraditional 3D printing based on Digital Light Processing Stereolithography (DLP-SL) is unnecessarily limiting as applied to microfluidic device fabrication, especially for high-resolution features. This limitation is due primarily to inherent tradeoffs between layer thickness, exposure time, material strength, and optical penetration that can be impossible to satisfy for microfluidic features. We introduce a generalized 3D printing process that significantly expands the accessible spatially distributed optical dose parameter space to enable the fabrication of much higher resolution 3D components without increasing the resolution of the 3D printer. Here we demonstrate component miniaturization in conjunction with a high degree of integration, including 15 μm × 15 μm valves and a 2.2 mm × 1.1 mm 10-stage 2-fold serial diluter. These results illustrate our approach’s promise to enable highly functional and compact microfluidic devices for a wide variety of biomolecular applications.
ADAR-mediated RNA editing of DNA:RNA hybrids is required for DNA double strand break repair
Authors: Jimeno Sonia , Prados-Carvajal Rosario , Fernández-Ávila María Jesús , Silva Sonia , Silvestris Domenico Alessandro , Endara-Coll Martín , Rodríguez-Real Guillermo , Domingo-Prim Judit , Mejías-Navarro Fernando , Romero-Franco Amador , Jimeno-González Silvia , Barroso Sonia , Cesarini Valeriana , Aguilera Andrés , Gallo Angela , Visa Neus , Huertas Pablo 
Published: September 2021

AbstractThe maintenance of genomic stability requires the coordination of multiple cellular tasks upon the appearance of DNA lesions. RNA editing, the post-transcriptional sequence alteration of RNA, has a profound effect on cell homeostasis, but its implication in the response to DNA damage was not previously explored. Here we show that, in response to DNA breaks, an overall change of the Adenosine-to-Inosine RNA editing is observed, a phenomenon we call the RNA Editing DAmage Response (REDAR). REDAR relies on the checkpoint kinase ATR and the recombination factor CtIP. Moreover, depletion of the RNA editing enzyme ADAR2 renders cells hypersensitive to genotoxic agents, increases genomic instability and hampers homologous recombination by impairing DNA resection. Such a role of ADAR2 in DNA repair goes beyond the recoding of specific transcripts, but depends on ADAR2 editing DNA:RNA hybrids to ease their dissolution.
Transverse barrier formation by electrical triggering of a metal-to-insulator transition
Authors: Salev Pavel , Fratino Lorenzo , Sasaki Dayne , Berkoun Rani , del Valle Javier , Kalcheim Yoav , Takamura Yayoi , Rozenberg Marcelo , Schuller Ivan K. 
Published: September 2021

AbstractApplication of an electric stimulus to a material with a metal-insulator transition can trigger a large resistance change. Resistive switching from an insulating into a metallic phase, which typically occurs by the formation of a conducting filament parallel to the current flow, is a highly active research topic. Using the magneto-optical Kerr imaging, we found that the opposite type of resistive switching, from a metal into an insulator, occurs in a reciprocal characteristic spatial pattern: the formation of an insulating barrier perpendicular to the driving current. This barrier formation leads to an unusual N-type negative differential resistance in the current-voltage characteristics. We further demonstrate that electrically inducing a transverse barrier enables a unique approach to voltage-controlled magnetism. By triggering the metal-to-insulator resistive switching in a magnetic material, local on/off control of ferromagnetism is achieved using a global voltage bias applied to the whole device.
METTL3-mediated m6A RNA methylation promotes the anti-tumour immunity of natural killer cells
Authors: Song Hao , Song Jiaxi , Cheng Ming , Zheng Meijuan , Wang Tian , Tian Sha , Flavell Richard A. , Zhu Shu , Li Hua-Bing , Ding Chen , Wei Haiming , Sun Rui , Peng Hui , Tian Zhigang 
Published: September 2021

AbstractNatural killer (NK) cells exert critical roles in anti-tumor immunity but how their functions are regulated by epitranscriptional modification (e.g., N6-methyladenosine (m6A) methylation) is unclear. Here we report decreased expression of the m6A “writer” METTL3 in tumor-infiltrating NK cells, and a positive correlation between protein expression levels of METTL3 and effector molecules in NK cells. Deletion of Mettl3 in NK cells alters the homeostasis of NK cells and inhibits NK cell infiltration and function in the tumor microenvironment, leading to accelerated tumor development and shortened survival in mice. The gene encoding SHP-2 is m6A modified, and its protein expression is decreased in METTL3-deficient NK cells. Reduced SHP-2 activity renders NK cells hyporesponsive to IL-15, which is associated with suppressed activation of the AKT and MAPK signaling pathway in METTL3-deficient NK cells. These findings show that m6A methylation safeguards the homeostasis and tumor immunosurveillance function of NK cells.
A method for intuitively extracting macromolecular dynamics from structural disorder
Authors: Pearce Nicholas M. , Gros Piet 
Published: September 2021

AbstractMacromolecular dynamics manifest as disorder in structure determination, which is subsequently accounted for by displacement parameters (also called temperature factors, or B-factors) or alternate conformations. Though B-factors contain detailed information about structural dynamics, they are the total of multiple sources of disorder, making them difficult to interpret and thus little-used in structural analysis. We report here an analytical approach for decomposing molecular disorder into a parsimonious hierarchical series of contributions, providing an intuitive basis for quantitative structural-dynamics analysis. We demonstrate the decomposition of disorder on example SARS-CoV-2 and STEAP4 structures, from both crystallographic and cryo-electron microscopy data, and reveal how understanding of the macromolecular disorder leads to deeper understanding of molecular motions and flexibility, and suggests hypotheses for molecular mechanisms.