bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards a global-scale soil climate mitigation strategy
Authors: Amelung W. , Bossio D. , de Vries W. , Kögel-Knabner I. , Lehmann J. , Amundson R. , Bol R. , Collins C. , Lal R. , Leifeld J. , Minasny B. , Pan G. , Paustian K. , Rumpel C. , Sanderman J. , van Groenigen J. W. , Mooney S. , van Wesemael B. , Wander M. , Chabbi A. 
Published: October 2020

AbstractSustainable soil carbon sequestration practices need to be rapidly scaled up and implemented to contribute to climate change mitigation. We highlight that the major potential for carbon sequestration is in cropland soils, especially those with large yield gaps and/or large historic soil organic carbon losses. The implementation of soil carbon sequestration measures requires a diverse set of options, each adapted to local soil conditions and management opportunities, and accounting for site-specific trade-offs. We propose the establishment of a soil information system containing localised information on soil group, degradation status, crop yield gap, and the associated carbon-sequestration potentials, as well as the provision of incentives and policies to translate management options into region- and soil-specific practices.
Global warming due to loss of large ice masses and Arctic summer sea ice
Authors: Wunderling Nico , Willeit Matteo , Donges Jonathan F. , Winkelmann Ricarda 
Published: October 2020

AbstractSeveral large-scale cryosphere elements such as the Arctic summer sea ice, the mountain glaciers, the Greenland and West Antarctic Ice Sheet have changed substantially during the last century due to anthropogenic global warming. However, the impacts of their possible future disintegration on global mean temperature (GMT) and climate feedbacks have not yet been comprehensively evaluated. Here, we quantify this response using an Earth system model of intermediate complexity. Overall, we find a median additional global warming of 0.43 °C (interquartile range: 0.39−0.46 °C) at a CO2 concentration of 400 ppm. Most of this response (55%) is caused by albedo changes, but lapse rate together with water vapour (30%) and cloud feedbacks (15%) also contribute significantly. While a decay of the ice sheets would occur on centennial to millennial time scales, the Arctic might become ice-free during summer within the 21st century. Our findings imply an additional increase of the GMT on intermediate to long time scales.
Capturing human categorization of natural images by combining deep networks and cognitive models
Authors: Battleday Ruairidh M. , Peterson Joshua C. , Griffiths Thomas L. 
Published: October 2020

AbstractHuman categorization is one of the most important and successful targets of cognitive modeling, with decades of model development and assessment using simple, low-dimensional artificial stimuli. However, it remains unclear how these findings relate to categorization in more natural settings, involving complex, high-dimensional stimuli. Here, we take a step towards addressing this question by modeling human categorization over a large behavioral dataset, comprising more than 500,000 judgments over 10,000 natural images from ten object categories. We apply a range of machine learning methods to generate candidate representations for these images, and show that combining rich image representations with flexible cognitive models captures human decisions best. We also find that in the high-dimensional representational spaces these methods generate, simple prototype models can perform comparably to the more complex memory-based exemplar models dominant in laboratory settings.
Genetically engineered magnetic nanocages for cancer magneto-catalytic theranostics
Authors: Zhang Yang , Wang Xiaoyong , Chu Chengchao , Zhou Zijian , Chen Biaoqi , Pang Xin , Lin Gan , Lin Huirong , Guo Yuxin , Ren En , Lv Peng , Shi Yesi , Zheng Qingbing , Yan Xiaohui , Chen Xiaoyuan , Liu Gang 
Published: October 2020

AbstractThe clinical applications of magnetic hyperthermia therapy (MHT) have been largely hindered by the poor magnetic-to-thermal conversion efficiency of MHT agents. Herein, we develop a facile and efficient strategy for engineering encapsulin-produced magnetic iron oxide nanocomposites (eMIONs) via a green biomineralization procedure. We demonstrate that eMIONs have excellent magnetic saturation and remnant magnetization properties, featuring superior magnetic-to-thermal conversion efficiency with an ultrahigh specific absorption rate of 2390 W/g to overcome the critical issues of MHT. We also show that eMIONs act as a nanozyme and have enhanced catalase-like activity in the presence of an alternative magnetic field, leading to tumor angiogenesis inhibition with a corresponding sharp decrease in the expression of HIF-1α. The inherent excellent magnetic-heat capability, coupled with catalysis-triggered tumor suppression, allows eMIONs to provide an MRI-guided magneto-catalytic combination therapy, which may open up a new avenue for bench-to-bed translational research of MHT.
Dispersion state phase diagram of citrate-coated metallic nanoparticles in saline solutions
Authors: Franco-Ulloa Sebastian , Tatulli Giuseppina , Bore Sigbjørn Løland , Moglianetti Mauro , Pompa Pier Paolo , Cascella Michele , De Vivo Marco 
Published: October 2020

AbstractThe fundamental interactions underlying citrate-mediated chemical stability of metal nanoparticles, and their surface characteristics dictating particle dispersion/aggregation in aqueous solutions, are largely unclear. Here, we developed a theoretical model to estimate the stoichiometry of small, charged ligands (like citrate) chemisorbed onto spherical metallic nanoparticles and coupled it with atomistic molecular dynamics simulations to define the uncovered solvent-accessible surface area of the nanoparticle. Then, we integrated coarse-grained molecular dynamics simulations and two-body free energy calculations to define dispersion state phase diagrams for charged metal nanoparticles in a range of medium’s ionic strength, a known trigger for aggregation. Ultraviolet-visible spectroscopy experiments of citrate-capped nanocolloids validated our predictions and extended our results to nanoparticles up to 35 nm. Altogether, our results disclose a complex interplay between the particle size, its surface charge density, and the ionic strength of the medium, which ultimately clarifies how these variables impact colloidal stability.
Circulating tumour DNA from the cerebrospinal fluid allows the characterisation and monitoring of medulloblastoma
Authors: Escudero Laura , Llort Anna , Arias Alexandra , Diaz-Navarro Ander , Martínez-Ricarte Francisco , Rubio-Perez Carlota , Mayor Regina , Caratù Ginevra , Martínez-Sáez Elena , Vázquez-Méndez Élida , Lesende-Rodríguez Iván , Hladun Raquel , Gros Luis , Ramón y Cajal Santiago , Poca Maria A. , Puente Xose S. , Sahuquillo Juan , Gallego Soledad , Seoane Joan 
Published: October 2020

AbstractThe molecular characterisation of medulloblastoma, the most common paediatric brain tumour, is crucial for the correct management and treatment of this heterogenous disease. However, insufficient tissue sample, the presence of tumour heterogeneity, or disseminated disease can challenge its diagnosis and monitoring. Here, we report that the cerebrospinal fluid (CSF) circulating tumour DNA (ctDNA) recapitulates the genomic alterations of the tumour and facilitates subgrouping and risk stratification, providing valuable information about diagnosis and prognosis. CSF ctDNA also characterises the intra-tumour genomic heterogeneity identifying small subclones. ctDNA is abundant in the CSF but barely present in plasma and longitudinal analysis of CSF ctDNA allows the study of minimal residual disease, genomic evolution and the characterisation of tumours at recurrence. Ultimately, CSF ctDNA analysis could facilitate the clinical management of medulloblastoma patients and help the design of tailored therapeutic strategies, increasing treatment efficacy while reducing excessive treatment to prevent long-term secondary effects.
Impact of wet-dry cycling on the phase behavior and compartmentalization properties of complex coacervates
Authors: Fares Hadi M. , Marras Alexander E. , Ting Jeffrey M. , Tirrell Matthew V. , Keating Christine D. 
Published: October 2020

AbstractWet-dry cycling on the early Earth is thought to have facilitated production of molecular building blocks of life, but its impact on self-assembly and compartmentalization remains largely unexplored. Here, we investigate dehydration/rehydration of complex coacervates, which are membraneless compartments formed by phase separation of polyelectrolyte solutions. Solution compositions are identified for which tenfold water loss results in maintenance, disappearance, or appearance of coacervate droplets. Systems maintaining coacervates throughout the dehydration process are further evaluated to understand how their compartmentalization properties change with drying. Although added total RNA concentrations increase tenfold, RNA concentration within coacervates remains steady. Exterior RNA concentrations rise, and exchange rates for encapsulated versus free RNAs increase with dehydration. We explain these results in light of the phase diagram, with dehydration-driven ionic strength increase being particularly important in determining coacervate properties. This work shows that wet-dry cycling can alter the phase behavior and protocell-relevant functions of complex coacervates.
Overcoming primary and acquired resistance to anti-PD-L1 therapy by induction and activation of tumor-residing cDC1s
Authors: Oba Takaaki , Long Mark D. , Keler Tibor , Marsh Henry C. , Minderman Hans , Abrams Scott I. , Liu Song , Ito Fumito 
Published: October 2020

AbstractThe ability of cancer cells to ensure T-cell exclusion from the tumor microenvironment is a significant mechanism of resistance to anti-PD-1/PD-L1 therapy. Evidence indicates crucial roles of Batf3-dependent conventional type-1 dendritic cells (cDC1s) for inducing antitumor T-cell immunity; however, strategies to maximize cDC1 engagement remain elusive. Here, using multiple orthotopic tumor mouse models resistant to anti-PD-L1-therapy, we are testing the hypothesis that in situ induction and activation of tumor-residing cDC1s overcomes poor T-cell infiltration. In situ immunomodulation with Flt3L, radiotherapy, and TLR3/CD40 stimulation induces an influx of stem-like Tcf1+ Slamf6+ CD8+ T cells, triggers regression not only of primary, but also untreated distant tumors, and renders tumors responsive to anti-PD-L1 therapy. Furthermore, serial in situ immunomodulation (ISIM) reshapes repertoires of intratumoral T cells, overcomes acquired resistance to anti-PD-L1 therapy, and establishes tumor-specific immunological memory. These findings provide new insights into cDC1 biology as a critical determinant to overcome mechanisms of intratumoral T-cell exclusion.
Neutrophil-induced ferroptosis promotes tumor necrosis in glioblastoma progression
Authors: Yee Patricia P. , Wei Yiju , Kim Soo-Yeon , Lu Tong , Chih Stephen Y. , Lawson Cynthia , Tang Miaolu , Liu Zhijun , Anderson Benjamin , Thamburaj Krishnamoorthy , Young Megan M. , Aregawi Dawit G. , Glantz Michael J. , Zacharia Brad E. , Specht Charles S. , Wang Hong-Gang , Li Wei 
Published: October 2020

AbstractTumor necrosis commonly exists and predicts poor prognoses in many cancers. Although it is thought to result from chronic ischemia, the underlying nature and mechanisms driving the involved cell death remain obscure. Here, we show that necrosis in glioblastoma (GBM) involves neutrophil-triggered ferroptosis. In a hyperactivated transcriptional coactivator with PDZ-binding motif-driven GBM mouse model, neutrophils coincide with necrosis temporally and spatially. Neutrophil depletion dampens necrosis. Neutrophils isolated from mouse brain tumors kill cocultured tumor cells. Mechanistically, neutrophils induce iron-dependent accumulation of lipid peroxides within tumor cells by transferring myeloperoxidase-containing granules into tumor cells. Inhibition or depletion of myeloperoxidase suppresses neutrophil-induced tumor cell cytotoxicity. Intratumoral glutathione peroxidase 4 overexpression or acyl-CoA synthetase long chain family member 4 depletion diminishes necrosis and aggressiveness of tumors. Furthermore, analyses of human GBMs support that neutrophils and ferroptosis are associated with necrosis and predict poor survival. Thus, our study identifies ferroptosis as the underlying nature of necrosis in GBMs and reveals a pro-tumorigenic role of ferroptosis. Together, we propose that certain tumor damage(s) occurring during early tumor progression (i.e. ischemia) recruits neutrophils to the site of tissue damage and thereby results in a positive feedback loop, amplifying GBM necrosis development to its fullest extent.
Modeling early stage atherosclerosis in a primary human vascular microphysiological system
Authors: Zhang Xu , Bishawi Muath , Zhang Ge , Prasad Varun , Salmon Ellen , Breithaupt Jason J. , Zhang Qiao , Truskey George A. 
Published: October 2020

AbstractNovel atherosclerosis models are needed to guide clinical therapy. Here, we report an in vitro model of early atherosclerosis by fabricating and perfusing multi-layer arteriole-scale human tissue-engineered blood vessels (TEBVs) by plastic compression. TEBVs maintain mechanical strength, vasoactivity, and nitric oxide (NO) production for at least 4 weeks. Perfusion of TEBVs at a physiological shear stress with enzyme-modified low-density-lipoprotein (eLDL) with or without TNFα promotes monocyte accumulation, reduces vasoactivity, alters NO production, which leads to endothelial cell activation, monocyte accumulation, foam cell formation and expression of pro-inflammatory cytokines. Removing eLDL leads to recovery of vasoactivity, but not loss of foam cells or recovery of permeability, while pretreatment with lovastatin or the P2Y11inhibitor NF157 reduces monocyte accumulation and blocks foam cell formation. Perfusion with blood leads to increased monocyte adhesion. This atherosclerosis model can identify the role of drugs on specific vascular functions that cannot be assessed in vivo.
Flow-induced order–order transitions in amyloid fibril liquid crystalline tactoids
Authors: Almohammadi Hamed , Bagnani Massimo , Mezzenga Raffaele 
Published: October 2020

AbstractLiquid crystalline droplets, also known as tactoids, forming by nucleation and growth within the phase diagram region where isotropic and nematic phases coexist, challenge our understanding of liquid crystals under confinement due to anisotropic surface boundaries at vanishingly small interfacial tension, resulting in complex, non-spherical shapes. Little is known about their dynamical properties, since they are mostly studied under quiescent, quasi-equilibrium conditions. Here we show that different classes of amyloid based nematic and cholesteric tactoids undergo order–order transitions by flow-induced deformations of their shape. Tactoids align under extensional flow, undergoing extreme deformation into highly elongated prolate shapes, with the cholesteric pitch decreasing as an inverse power-law of the tactoids aspect ratio. Free energy functional theory and experimental measurements are combined to rationalize the critical elongation above which the director-field configuration of tactoids transforms from bipolar and uniaxial cholesteric to homogenous and to debate on the thermodynamic nature of these transitions.
Force-clamp spectroscopy identifies a catch bond mechanism in a Gram-positive pathogen
Authors: Mathelié-Guinlet Marion , Viela Felipe , Pietrocola Giampiero , Speziale Pietro , Alsteens David , Dufrêne Yves F. 
Published: October 2020

AbstractPhysical forces have profound effects on cellular behavior, physiology, and disease. Perhaps the most intruiguing and fascinating example is the formation of catch-bonds that strengthen cellular adhesion under shear stresses. Today mannose-binding by the Escherichia coli FimH adhesin remains one of the rare microbial catch-bond thoroughly characterized at the molecular level. Here we provide a quantitative demonstration of a catch-bond in living Gram-positive pathogens using force-clamp spectroscopy. We show that the dock, lock, and latch interaction between staphylococcal surface protein SpsD and fibrinogen is strong, and exhibits an unusual catch-slip transition. The bond lifetime first grows with force, but ultimately decreases to behave as a slip bond beyond a critical force (~1 nN) that is orders of magnitude higher than for previously investigated complexes. This catch-bond, never reported for a staphylococcal adhesin, provides the pathogen with a mechanism to tightly control its adhesive function during colonization and infection.
A protein tertiary structure mimetic modulator of the Hippo signalling pathway
Authors: Adihou Hélène , Gopalakrishnan Ranganath , Förster Tim , Guéret Stéphanie M. , Gasper Raphael , Geschwindner Stefan , Carrillo García Carmen , Karatas Hacer , Pobbati Ajaybabu V. , Vazquez‐Chantada Mercedes , Davey Paul , Wassvik Carola M. , Pang Jeremy Kah Sheng , Soh Boon Seng , Hong Wanjin , Chiarparin Elisabetta , Schade Dennis , Plowright Alleyn T. , Valeur Eric , Lemurell Malin , Grossmann Tom N. , Waldmann Herbert 
Published: October 2020

AbstractTranscription factors are key protein effectors in the regulation of gene transcription, and in many cases their activity is regulated via a complex network of protein–protein interactions (PPI). The chemical modulation of transcription factor activity is a long-standing goal in drug discovery but hampered by the difficulties associated with the targeting of PPIs, in particular when extended and flat protein interfaces are involved. Peptidomimetics have been applied to inhibit PPIs, however with variable success, as for certain interfaces the mimicry of a single secondary structure element is insufficient to obtain high binding affinities. Here, we describe the design and characterization of a stabilized protein tertiary structure that acts as an inhibitor of the interaction between the transcription factor TEAD and its co-repressor VGL4, both playing a central role in the Hippo signalling pathway. Modification of the inhibitor with a cell-penetrating entity yielded a cell-permeable proteomimetic that activates cell proliferation via regulation of the Hippo pathway, highlighting the potential of protein tertiary structure mimetics as an emerging class of PPI modulators.
Local community assembly mechanisms shape soil bacterial β diversity patterns along a latitudinal gradient
Authors: Zhang Xiao , Liu Shirong , Wang Jingxin , Huang Yongtao , Freedman Zachary , Fu Shenglei , Liu Kuan , Wang Hui , Li Xiangzhen , Yao Minjie , Liu Xiaojing , Schuler Jamie 
Published: October 2020

AbstractBiodiversity patterns across geographical gradients could result from regional species pool and local community assembly mechanisms. However, little has been done to separate the effects of local ecological mechanisms from variation in the regional species pools on bacterial diversity patterns. In this study, we compare assembly mechanisms of soil bacterial communities in 660 plots from 11 regions along a latitudinal gradient in eastern China with highly divergent species pools. Our results show that β diversity does not co-vary with γ diversity, and local community assembly mechanisms appear to explain variation in β diversity patterns after correcting for variation in regional species pools. The variation in environmental conditions along the latitudinal gradient accounts for the variation in β diversity through mediating the strength of heterogeneous selection. In conclusion, our study clearly illustrates the importance of local community assembly processes in shaping geographical patterns of soil bacterial β diversity.
Disease burden and clinical severity of the first pandemic wave of COVID-19 in Wuhan, China
Authors: Yang Juan , Chen Xinhua , Deng Xiaowei , Chen Zhiyuan , Gong Hui , Yan Han , Wu Qianhui , Shi Huilin , Lai Shengjie , Ajelli Marco , Viboud Cecile , Yu Prof Hongjie 
Published: October 2020

AbstractThe novel coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China, where the initial wave of intense community transmissions was cut short by interventions. Using multiple data sources, here we estimate the disease burden and clinical severity by age of COVID-19 in Wuhan from December 1, 2019 to March 31, 2020. Our estimates account for the sensitivity of the laboratory assays, prospective community screenings, and healthcare seeking behaviors. Rates of symptomatic cases, medical consultations, hospitalizations and deaths were estimated at 796 (95% CI: 703–977), 489 (472–509), 370 (358–384), and 36.2 (35.0–37.3) per 100,000 persons, respectively. The COVID-19 outbreak in Wuhan had a higher burden than the 2009 influenza pandemic or seasonal influenza in terms of hospitalization and mortality rates, and clinical severity was similar to that of the 1918 influenza pandemic. Our comparison puts the COVID-19 pandemic into context and could be helpful to guide intervention strategies and preparedness for the potential resurgence of COVID-19.
Structure of human steroid 5α-reductase 2 with the anti-androgen drug finasteride
Authors: Xiao Qingpin , Wang Lei , Supekar Shreyas , Shen Tao , Liu Heng , Ye Fei , Huang Junzhou , Fan Hao , Wei Zhiyi , Zhang Cheng 
Published: October 2020

AbstractHuman steroid 5α-reductase 2 (SRD5A2) is an integral membrane enzyme in steroid metabolism and catalyzes the reduction of testosterone to dihydrotestosterone. Mutations in theSRD5A2gene have been linked to 5α-reductase deficiency and prostate cancer. Finasteride and dutasteride, as SRD5A2 inhibitors, are widely used antiandrogen drugs for benign prostate hyperplasia. The molecular mechanisms underlying enzyme catalysis and inhibition for SRD5A2 and other eukaryotic integral membrane steroid reductases remain elusive due to a lack of structural information. Here, we report a crystal structure of human SRD5A2 at 2.8 Å, revealing a unique 7-TM structural topology and an intermediate adduct of finasteride and NADPH as NADP-dihydrofinasteride in a largely enclosed binding cavity inside the transmembrane domain. Structural analysis together with computational and mutagenesis studies reveal the molecular mechanisms of the catalyzed reaction and of finasteride inhibition involving residues E57 and Y91. Molecular dynamics simulation results indicate high conformational dynamics of the cytosolic region that regulate NADPH/NADP+exchange. Mapping disease-causing mutations of SRD5A2 to our structure suggests molecular mechanisms for their pathological effects. Our results offer critical structural insights into the function of integral membrane steroid reductases and may facilitate drug development.