bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct contribution of skeletal muscle mesenchymal progenitors to bone repair
Authors: Julien Anais , Kanagalingam Anuya , Martínez-Sarrà Ester , Megret Jérome , Luka Marine , Ménager Mickaël , Relaix Frédéric , Colnot Céline 
Published: May 2021

AbstractBone regenerates by activation of tissue resident stem/progenitor cells, formation of a fibrous callus followed by deposition of cartilage and bone matrices. Here, we show that mesenchymal progenitors residing in skeletal muscle adjacent to bone mediate the initial fibrotic response to bone injury and also participate in cartilage and bone formation. Combined lineage and single-cell RNA sequencing analyses reveal that skeletal muscle mesenchymal progenitors adopt a fibrogenic fate before they engage in chondrogenesis after fracture. In polytrauma, where bone and skeletal muscle are injured, skeletal muscle mesenchymal progenitors exhibit altered fibrogenesis and chondrogenesis. This leads to impaired bone healing, which is due to accumulation of fibrotic tissue originating from skeletal muscle and can be corrected by the anti-fibrotic agent Imatinib. These results elucidate the central role of skeletal muscle in bone regeneration and provide evidence that skeletal muscle can be targeted to prevent persistent callus fibrosis and improve bone healing after musculoskeletal trauma.
Longitudinal single-cell profiling reveals molecular heterogeneity and tumor-immune evolution in refractory mantle cell lymphoma
Authors: Zhang Shaojun , Jiang Vivian Changying , Han Guangchun , Hao Dapeng , Lian Junwei , Liu Yang , Cai Qingsong , Zhang Rongjia , McIntosh Joseph , Wang Ruiping , Dang Minghao , Dai Enyu , Wang Yuanxin , Santos David , Badillo Maria , Leeming Angela , Chen Zhihong , Hartig Kimberly , Bigcal John , Zhou Jia , Kanagal-Shamanna Rashmi , Ok Chi Young , Lee Hun , Steiner Raphael E. , Zhang Jianhua , Song Xingzhi , Nair Ranjit , Ahmed Sairah , Rodriquez Alma , Thirumurthi Selvi , Jain Preetesh , Wagner-Bartak Nicolaus , Hill Holly , Nomie Krystle , Flowers Christopher , Futreal Andrew , Wang Linghua , Wang Michael 
Published: May 2021

AbstractThe mechanisms driving therapeutic resistance and poor outcomes of mantle cell lymphoma (MCL) are incompletely understood. We characterize the cellular and molecular heterogeneity within and across patients and delineate the dynamic evolution of tumor and immune cell compartments at single cell resolution in longitudinal specimens from ibrutinib-sensitive patients and non-responders. Temporal activation of multiple cancer hallmark pathways and acquisition of 17q are observed in a refractory MCL. Multi-platform validation is performed at genomic and cellular levels in PDX models and larger patient cohorts. We demonstrate that due to 17q gain, BIRC5/survivin expression is upregulated in resistant MCL tumor cells and targeting BIRC5 results in marked tumor inhibition in preclinical models. In addition, we discover notable differences in the tumor microenvironment including progressive dampening of CD8+ T cells and aberrant cell-to-cell communication networks in refractory MCLs. This study reveals diverse and dynamic tumor and immune programs underlying therapy resistance in MCL.
The neutrotime transcriptional signature defines a single continuum of neutrophils across biological compartments
Authors: Grieshaber-Bouyer Ricardo , Radtke Felix A. , Cunin Pierre , Stifano Giuseppina , Levescot Anaïs , Vijaykumar Brinda , Nelson-Maney Nathan , Blaustein Rachel B. , Monach Paul A. , Nigrovic Peter A. ,   ImmGen Consortium, Aguilar Oscar , Allan Rhys , Astarita Jilian , Austen K. Frank , Barrett Nora , Baysoy Alev , Benoist Christophe , Brown Brian D. , Buechler Matthew , Buenrostro Jason , Casanova Maria Acebes , Chowdhary Kaitavjeet , Colonna Marco , Crowl Ty , Deng Tianda , Desland Fiona , Dhainaut Maxime , Ding Jiarui , Dominguez Claudia , Dwyer Daniel , Frascoli Michela , Gal-Oz Shani , Goldrath Ananda , Johanson Tim , Jordan Stefan , Kang Joonsoo , Kapoor Varun , Kenigsberg Ephraim , Kim Joel , Kim Ki wook , Kiner Evgeny , Kronenberg Mitchell , Lanier Lewis , Laplace Catherine , Lareau Caleb , Leader Andrew , Lee Jisu , Magen Assaf , Maier Barbara , Maslova Alexandra , Mathis Diane , McFarland Adelle , Merad Miriam , Meunier Etienne , Monach Paul A. , Mostafavi Sara , Muller Soren , Muus Christoph , Ner-Gaon Hadas , Nguyen Quyhn , Novakovsky German , Nutt Stephen , Omilusik Kayla , Ortiz-Lopez Adriana , Paynich Mallory , Peng Vincent , Potempa Marc , Pradhan Rachana , Quon Sara , Ramirez Ricardo , Ramanan Deepshika , Randolph Gwendalyn , Regev Aviv , Rose Samuel A. , Seddu Kumba , Shay Tal , Shemesh Avishai , Shyer Justin , Smilie Christopher , Spidale Nick , Subramanian Ayshwarya , Sylvia Katelyn , Tellier Julie , Turley Shannon , Vijaykumar Brinda , Wagers Amy , Wang Chendi , Wang Peter L. , Wroblewska Aleksandra , Yang Liang , Yim Aldrin , Yoshida Hideyuki 
Published: May 2021

AbstractNeutrophils are implicated in multiple homeostatic and pathological processes, but whether functional diversity requires discrete neutrophil subsets is not known. Here, we apply single-cell RNA sequencing to neutrophils from normal and inflamed mouse tissues. Whereas conventional clustering yields multiple alternative organizational structures, diffusion mapping plus RNA velocity discloses a single developmental spectrum, ordered chronologically. Termed here neutrotime, this spectrum extends from immature pre-neutrophils, largely in bone marrow, to mature neutrophils predominantly in blood and spleen. The sharpest increments in neutrotime occur during the transitions from pre-neutrophils to immature neutrophils and from mature marrow neutrophils to those in blood. Human neutrophils exhibit a similar transcriptomic pattern. Neutrophils migrating into inflamed mouse lung, peritoneum and joint maintain the core mature neutrotime signature together with new transcriptional activity that varies with site and stimulus. Together, these data identify a single developmental spectrum as the dominant organizational theme of neutrophil heterogeneity.
EMX2-GPR156-Gαi reverses hair cell orientation in mechanosensory epithelia
Authors: Kindt Katie S. , Akturk Anil , Jarysta Amandine , Day Matthew , Beirl Alisha , Flonard Michaela , Tarchini Basile 
Published: May 2021

AbstractHair cells detect sound, head position or water movements when their mechanosensory hair bundle is deflected. Each hair bundle has an asymmetric architecture that restricts stimulus detection to a single axis. Coordinated hair cell orientations within sensory epithelia further tune stimulus detection at the organ level. Here, we identify GPR156, an orphan GPCR of unknown function, as a critical regulator of hair cell orientation. We demonstrate that the transcription factor EMX2 polarizes GPR156 distribution, enabling it to signal through Gαi and trigger a 180° reversal in hair cell orientation. GPR156-Gαi mediated reversal is essential to establish hair cells with mirror-image orientations in mouse otolith organs in the vestibular system and in zebrafish lateral line. Remarkably, GPR156-Gαi also instructs hair cell reversal in the auditory epithelium, despite a lack of mirror-image organization. Overall, our work demonstrates that conserved GPR156-Gαi signaling is integral to the framework that builds directional responses into mechanosensory epithelia.
Demonstration of a compact plasma accelerator powered by laser-accelerated electron beams
Authors: Kurz T. , Heinemann T. , Gilljohann M. F. , Chang Y. Y. , Couperus Cabadağ J. P. , Debus A. , Kononenko O. , Pausch R. , Schöbel S. , Assmann R. W. , Bussmann M. , Ding H. , Götzfried J. , Köhler A. , Raj G. , Schindler S. , Steiniger K. , Zarini O. , Corde S. , Döpp A. , Hidding B. , Karsch S. , Schramm U. , Martinez de la Ossa A. , Irman A. 
Published: May 2021

AbstractPlasma wakefield accelerators are capable of sustaining gigavolt-per-centimeter accelerating fields, surpassing the electric breakdown threshold in state-of-the-art accelerator modules by 3-4 orders of magnitude. Beam-driven wakefields offer particularly attractive conditions for the generation and acceleration of high-quality beams. However, this scheme relies on kilometer-scale accelerators. Here, we report on the demonstration of a millimeter-scale plasma accelerator powered by laser-accelerated electron beams. We showcase the acceleration of electron beams to 128 MeV, consistent with simulations exhibiting accelerating gradients exceeding 100 GV m−1. This miniaturized accelerator is further explored by employing a controlled pair of drive and witness electron bunches, where a fraction of the driver energy is transferred to the accelerated witness through the plasma. Such a hybrid approach allows fundamental studies of beam-driven plasma accelerator concepts at widely accessible high-power laser facilities. It is anticipated to provide compact sources of energetic high-brightness electron beams for quality-demanding applications such as free-electron lasers.
TRPM7 kinase-mediated immunomodulation in macrophage plays a central role in magnesium ion-induced bone regeneration
Authors: Qiao Wei , Wong Karen H. M. , Shen Jie , Wang Wenhao , Wu Jun , Li Jinhua , Lin Zhengjie , Chen Zetao , Matinlinna Jukka P. , Zheng Yufeng , Wu Shuilin , Liu Xuanyong , Lai Keng Po , Chen Zhuofan , Lam Yun Wah , Cheung Kenneth M. C. , Yeung Kelvin W. K. 
Published: May 2021

AbstractDespite the widespread observations on the osteogenic effects of magnesium ion (Mg2+), the diverse roles of Mg2+ during bone healing have not been systematically dissected. Here, we reveal a previously unknown, biphasic mode of action of Mg2+ in bone repair. During the early inflammation phase, Mg2+ contributes to an upregulated expression of transient receptor potential cation channel member 7 (TRPM7), and a TRPM7-dependent influx of Mg2+ in the monocyte-macrophage lineage, resulting in the cleavage and nuclear accumulation of TRPM7-cleaved kinase fragments (M7CKs). This then triggers the phosphorylation of Histone H3 at serine 10, in a TRPM7-dependent manner at the promoters of inflammatory cytokines, leading to the formation of a pro-osteogenic immune microenvironment. In the later remodeling phase, however, the continued exposure of Mg2+ not only lead to the over-activation of NF-κB signaling in macrophages and increased number of osteoclastic-like cells but also decelerates bone maturation through the suppression of hydroxyapatite precipitation. Thus, the negative effects of Mg2+ on osteogenesis can override the initial pro-osteogenic benefits of Mg2+. Taken together, this study establishes a paradigm shift in the understanding of the diverse and multifaceted roles of Mg2+ in bone healing.
Health and sustainability of glaciers in High Mountain Asia
Authors: Miles Evan , McCarthy Michael , Dehecq Amaury , Kneib Marin , Fugger Stefan , Pellicciotti Francesca 
Published: May 2021

AbstractGlaciers in High Mountain Asia generate meltwater that supports the water needs of 250 million people, but current knowledge of annual accumulation and ablation is limited to sparse field measurements biased in location and glacier size. Here, we present altitudinally-resolved specific mass balances (surface, internal, and basal combined) for 5527 glaciers in High Mountain Asia for 2000–2016, derived by correcting observed glacier thinning patterns for mass redistribution due to ice flow. We find that 41% of glaciers accumulated mass over less than 20% of their area, and only 60% ± 10% of regional annual ablation was compensated by accumulation. Even without 21stcentury warming, 21% ± 1% of ice volume will be lost by 2100 due to current climatic-geometric imbalance, representing a reduction in glacier ablation into rivers of 28% ± 1%. The ablation of glaciers in the Himalayas and Tien Shan was mostly unsustainable and ice volume in these regions will reduce by at least 30% by 2100. The most important and vulnerable glacier-fed river basins (Amu Darya, Indus, Syr Darya, Tarim Interior) were supplied with >50% sustainable glacier ablation but will see long-term reductions in ice mass and glacier meltwater supply regardless of the Karakoram Anomaly.
Longitudinal in vivo imaging of acute neuropathology in a monkey model of Ebola virus infection
Authors: Schreiber-Stainthorp William , Solomon Jeffrey , Lee Ji Hyun , Castro Marcelo , Shah Swati , Martinez-Orengo Neysha , Reeder Rebecca , Maric Dragan , Gross Robin , Qin Jing , Hagen Katie R. , Johnson Reed F. , Hammoud Dima A. 
Published: May 2021

AbstractEbola virus (EBOV) causes neurological symptoms yet its effects on the central nervous system (CNS) are not well-described. Here, we longitudinally assess the acute effects of EBOV on the brain, using quantitative MR-relaxometry, 18F-Fluorodeoxyglucose PET and immunohistochemistry in a monkey model. We report blood–brain barrier disruption, likely related to high cytokine levels and endothelial viral infection, with extravasation of fluid, Gadolinium-based contrast material and albumin into the extracellular space. Increased glucose metabolism is also present compared to the baseline, especially in the deep gray matter and brainstem. This regional hypermetabolism corresponds with mild neuroinflammation, sporadic neuronal infection and apoptosis, as well as increased GLUT3 expression, consistent with increased neuronal metabolic demands. Neuroimaging changes are associated with markers of disease progression including viral load and cytokine/chemokine levels. Our results provide insight into the pathophysiology of CNS involvement with EBOV and may help assess vaccine/treatment efficacy in real time.
A global resource for genomic predictions of antimicrobial resistance and surveillance of Salmonella Typhi at pathogenwatch
Authors: Argimón Silvia , Yeats Corin A. , Goater Richard J. , Abudahab Khalil , Taylor Benjamin , Underwood Anthony , Sánchez-Busó Leonor , Wong Vanessa K. , Dyson Zoe A. , Nair Satheesh , Park Se Eun , Marks Florian , Page Andrew J. , Keane Jacqueline A. , Baker Stephen , Holt Kathryn E. , Dougan Gordon , Aanensen David M. 
Published: May 2021

AbstractAs whole-genome sequencing capacity becomes increasingly decentralized, there is a growing opportunity for collaboration and the sharing of surveillance data within and between countries to inform typhoid control policies. This vision requires free, community-driven tools that facilitate access to genomic data for public health on a global scale. Here we present the Pathogenwatch scheme for Salmonella enterica serovar Typhi (S. Typhi), a web application enabling the rapid identification of genomic markers of antimicrobial resistance (AMR) and contextualization with public genomic data. We show that the clustering of S. Typhi genomes in Pathogenwatch is comparable to established bioinformatics methods, and that genomic predictions of AMR are highly concordant with phenotypic susceptibility data. We demonstrate the public health utility of Pathogenwatch with examples selected from >4,300 public genomes available in the application. Pathogenwatch provides an intuitive entry point to monitor of the emergence and spread of S. Typhi high risk clones.
Electrochemical ammonia synthesis via nitrate reduction on Fe single atom catalyst
Authors: Wu Zhen-Yu , Karamad Mohammadreza , Yong Xue , Huang Qizheng , Cullen David A. , Zhu Peng , Xia Chuan , Xiao Qunfeng , Shakouri Mohsen , Chen Feng-Yang , Kim Jung Yoon , Xia Yang , Heck Kimberly , Hu Yongfeng , Wong Michael S. , Li Qilin , Gates Ian , Siahrostami Samira , Wang Haotian 
Published: May 2021

AbstractElectrochemically converting nitrate, a widespread water pollutant, back to valuable ammonia is a green and delocalized route for ammonia synthesis, and can be an appealing and supplementary alternative to the Haber-Bosch process. However, as there are other nitrate reduction pathways present, selectively guiding the reaction pathway towards ammonia is currently challenged by the lack of efficient catalysts. Here we report a selective and active nitrate reduction to ammonia on Fe single atom catalyst, with a maximal ammonia Faradaic efficiency of ~ 75% and a yield rate of up to ~ 20,000 μg h−1 mgcat.−1 (0.46 mmol h−1 cm−2). Our Fe single atom catalyst can effectively prevent the N-N coupling step required for N2 due to the lack of neighboring metal sites, promoting ammonia product selectivity. Density functional theory calculations reveal the reaction mechanisms and the potential limiting steps for nitrate reduction on atomically dispersed Fe sites.
Net decrease in spine-surface GluA1-containing AMPA receptors after post-learning sleep in the adult mouse cortex
Authors: Miyamoto Daisuke , Marshall William , Tononi Giulio , Cirelli Chiara 
Published: May 2021

AbstractThe mechanisms by which sleep benefits learning and memory remain unclear. Sleep may further strengthen the synapses potentiated by learning or promote broad synaptic weakening while protecting the newly potentiated synapses. We tested these ideas by combining a motor task whose consolidation is sleep-dependent, a marker of synaptic AMPA receptor plasticity, and repeated two-photon imaging to track hundreds of spines in vivo with single spine resolution. In mouse motor cortex, sleep leads to an overall net decrease in spine-surface GluA1-containing AMPA receptors, both before and after learning. Molecular changes in single spines during post-learning sleep are correlated with changes in performance after sleep. The spines in which learning leads to the largest increase in GluA1 expression have a relative advantage after post-learning sleep compared to sleep deprivation, because sleep weakens all remaining spines. These results are obtained in adult mice, showing that sleep-dependent synaptic down-selection also benefits the mature brain.
Single-cell lipidomics with high structural specificity by mass spectrometry
Authors: Li Zishuai , Cheng Simin , Lin Qiaohong , Cao Wenbo , Yang Jing , Zhang Minmin , Shen Aijun , Zhang Wenpeng , Xia Yu , Ma Xiaoxiao , Ouyang Zheng 
Published: May 2021

AbstractSingle-cell analysis is critical to revealing cell-to-cell heterogeneity that would otherwise be lost in ensemble analysis. Detailed lipidome characterization for single cells is still far from mature, especially when considering the highly complex structural diversity of lipids and the limited sample amounts available from a single cell. We report the development of a general strategy enabling single-cell lipidomic analysis with high structural specificity. Cell fixation is applied to retain lipids in the cell during batch treatments prior to single-cell analysis. In addition to tandem mass spectrometry analysis revealing the class and fatty acyl-chain for lipids, batch photochemical derivatization and single-cell droplet treatment are performed to identify the C=C locations and sn-positions of lipids, respectively. Electro-migration combined with droplet-assisted electrospray ionization enables single-cell mass spectrometry analysis with easy operation but high efficiency in sample usage. Four subtypes of human breast cancer cells are correctly classified through quantitative analysis of lipid C=C location or sn-position isomers in ~160 cells. Most importantly, the single-cell deep lipidomics strategy successfully discriminates gefitinib-resistant cells from a population of wild-type human lung cancer cells (HCC827), highlighting its unique capability to promote precision medicine.
Efficient 3D printing via photooxidation of ketocoumarin based photopolymerization
Authors: Zhao Xiaoyu , Zhao Ye , Li Ming-De , Li Zhong’an , Peng Haiyan , Xie Tao , Xie Xiaolin 
Published: May 2021

AbstractPhotopolymerization-based three-dimensional (3D) printing can enable customized manufacturing that is difficult to achieve through other traditional means. Nevertheless, it remains challenging to achieve efficient 3D printing due to the compromise between print speed and resolution. Herein, we report an efficient 3D printing approach based on the photooxidation of ketocoumarin that functions as the photosensitizer during photopolymerization, which can simultaneously deliver high print speed (5.1 cm h−1) and high print resolution (23 μm) on a common 3D printer. Mechanistically, the initiating radical and deethylated ketocoumarin are both generated upon visible light exposure, with the former giving rise to rapid photopolymerization and high print speed while the latter ensuring high print resolution by confining the light penetration. By comparison, the printed feature is hard to identify when the ketocoumarin encounters photoreduction due to the increased lateral photopolymerization. The proposed approach here provides a viable solution towards efficient additive manufacturing by controlling the photoreaction of photosensitizers during photopolymerization.
IL-21 and IFNα therapy rescues terminally differentiated NK cells and limits SIV reservoir in ART-treated macaques
Authors: Harper Justin , Huot Nicolas , Micci Luca , Tharp Gregory , King Colin , Rascle Philippe , Shenvi Neeta , Wang Hong , Galardi Cristin , Upadhyay Amit A. , Villinger Francois , Lifson Jeffrey , Silvestri Guido , Easley Kirk , Jacquelin Beatrice , Bosinger Steven , Müller-Trutwin Michaela , Paiardini Mirko 
Published: May 2021

AbstractUnlike HIV infection, which progresses to AIDS absent suppressive anti-retroviral therapy, nonpathogenic infections in natural hosts, such African green monkeys, are characterized by a lack of gut microbial translocation and robust secondary lymphoid natural killer cell responses resulting in an absence of chronic inflammation and limited SIV dissemination in lymph node B-cell follicles. Here we report, using the pathogenic model of antiretroviral therapy-treated, SIV-infected rhesus macaques that sequential interleukin-21 and interferon alpha therapy generate terminally differentiated blood natural killer cells (NKG2a/clowCD16+) with potent human leukocyte antigen-E-restricted activity in response to SIV envelope peptides. This is in contrast to control macaques, where less differentiated, interferon gamma-producing natural killer cells predominate. The frequency and activity of terminally differentiated NKG2a/clowCD16+natural killer cells correlates with a reduction of replication-competent SIV in lymph node during antiretroviral therapy and time to viral rebound following analytical treatment interruption. These data demonstrate that African green monkey-like natural killer cell differentiation profiles can be rescued in rhesus macaques to promote viral clearance in tissues.
A universal strategy towards high–energy aqueous multivalent–ion batteries
Authors: Tang Xiao , Zhou Dong , Zhang Bao , Wang Shijian , Li Peng , Liu Hao , Guo Xin , Jaumaux Pauline , Gao Xiaochun , Fu Yongzhu , Wang Chengyin , Wang Chunsheng , Wang Guoxiu 
Published: May 2021

AbstractRechargeable multivalent metal (e.g., Ca, Mg or, Al) batteries are ideal candidates for large–scale electrochemical energy storage due to their intrinsic low cost. However, their practical application is hampered by the low electrochemical reversibility, dendrite growth at the metal anodes, sluggish multivalent–ion kinetics in metal oxide cathodes and, poor electrode compatibility with non–aqueous organic–based electrolytes. To circumvent these issues, here we report various aqueous multivalent–ion batteries comprising of concentrated aqueous gel electrolytes, sulfur–containing anodes and, high-voltage metal oxide cathodes as alternative systems to the non–aqueous multivalent metal batteries. This rationally designed aqueous battery chemistry enables satisfactory specific energy, favorable reversibility and improved safety. As a demonstration model, we report a room–temperature calcium-ion/sulfur| |metal oxide full cell with a specific energy of 110 Wh kg–1 and remarkable cycling stability. Molecular dynamics modeling and experimental investigations reveal that the side reactions could be significantly restrained through the suppressed water activity and formation of a protective inorganic solid electrolyte interphase. The unique redox chemistry of the multivalent–ion system is also demonstrated for aqueous magnesium–ion/sulfur||metal oxide and aluminum–ion/sulfur||metal oxide full cells.