bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of an ASC oligomerization inhibitor for the treatment of inflammatory diseases
Authors: Soriano-Teruel Paula M. , García‑Laínez Guillermo , Marco-Salvador María , Pardo Julián , Arias Maykel , DeFord Christian , Merfort Irmgard , Vicent María J. , Pelegrín Pablo , Sancho Mónica , Orzáez Mar 
Published: December 2021

AbstractThe ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain (CARD)) protein is an scaffold component of different inflammasomes, intracellular multiprotein platforms of the innate immune system that are activated in response to pathogens or intracellular damage. The formation of ASC specks, initiated by different inflammasome receptors, promotes the recruitment and activation of procaspase-1, thereby triggering pyroptotic inflammatory cell death and pro-inflammatory cytokine release. Here we describe MM01 as the first-in-class small-molecule inhibitor of ASC that interferes with ASC speck formation. MM01 inhibition of ASC oligomerization prevents activation of procaspase-1 in vitro and inhibits the activation of different ASC-dependent inflammasomes in cell lines and primary cultures. Furthermore, MM01 inhibits inflammation in vivo in a mouse model of inflammasome-induced peritonitis. Overall, we highlight MM01 as a novel broad-spectrum inflammasome inhibitor for the potential treatment of multifactorial diseases involving the dysregulation of multiple inflammasomes.
Natural history of NF1 c.2970_2972del p.(Met992del): confirmation of a low risk of complications in a longitudinal study
Authors: Forde Claire , Burkitt-Wright Emma , Turnpenny Peter D. , Haan Eric , Ealing John , Mansour Sahar , Holder Muriel , Lahiri Nayana , Dixit Abhijit , Procter Annie , Pacot Laurence , Vidaud Dominique , Capri Yline , Gerard Marion , Dollfus Hélène , Schaefer Elise , Quelin Chloé , Sigaudy Sabine , Busa Tiffany , Vera Gabriella , Damaj Lena , Messiaen Ludwine , Stevenson David A. , Davies Peter , Palmer-Smith Sheila , Callaway Alison , Wolkenstein Pierre , Pasmant Eric , Upadhyaya Meena 
Published: December 2021

AbstractIndividuals with the three base pair deletion NM_000267.3(NF1):c.2970_2972del p.(Met992del) have been recognised to present with a milder neurofibromatosis type 1 (NF1) phenotype characterised by café-au-lait macules (CALs) and intertriginous freckling, as well as a lack of cutaneous, subcutaneous and plexiform neurofibromas and other NF1-associated complications. Examining large cohorts of patients over time with this specific genotype is important to confirm the presentation and associated risks of this variant across the lifespan. Forty-one individuals with the in-frame NF1 deletion p.Met992del were identified from 31 families. Clinicians completed a standardised clinical questionnaire for each patient and the resulting data were collated and compared to published cohorts. Thirteen patients have been previously reported, and updated clinical information has been obtained for these individuals. Both CALs and intertriginous freckling were present in the majority of individuals (26/41, 63%) and the only confirmed features in 11 (27%). 34/41 (83%) of the cohort met NIH diagnostic criteria. There was a notable absence of all NF1-associated tumour types (neurofibroma and glioma). Neurofibroma were observed in only one individual—a subcutaneous lesion (confirmed histologically). Nineteen individuals were described as having a learning disability (46%). This study confirms that individuals with p.Met992del display a mild tumoural phenotype compared to those with ‘classical’, clinically diagnosed NF1, and this appears to be the case longitudinally through time as well as at presentation. Learning difficulties, however, appear to affect a significant proportion of NF1 subjects with this phenotype. Knowledge of this genotype–phenotype association is fundamental to accurate prognostication for families and caregivers.
Time-resolved cryo-EM visualizes ribosomal translocation with EF-G and GTP
Authors: Carbone Christine E. , Loveland Anna B. , Gamper Howard B. , Hou Ya-Ming , Demo Gabriel , Korostelev Andrei A. 
Published: December 2021

AbstractDuring translation, a conserved GTPase elongation factor—EF-G in bacteria or eEF2 in eukaryotes—translocates tRNA and mRNA through the ribosome. EF-G has been proposed to act as a flexible motor that propels tRNA and mRNA movement, as a rigid pawl that biases unidirectional translocation resulting from ribosome rearrangements, or by various combinations of motor- and pawl-like mechanisms. Using time-resolved cryo-EM, we visualized GTP-catalyzed translocation without inhibitors, capturing elusive structures of ribosome•EF-G intermediates at near-atomic resolution. Prior to translocation, EF-G binds near peptidyl-tRNA, while the rotated 30S subunit stabilizes the EF-G GTPase center. Reverse 30S rotation releases Pi and translocates peptidyl-tRNA and EF-G by ~20 Å. An additional 4-Å translocation initiates EF-G dissociation from a transient ribosome state with highly swiveled 30S head. The structures visualize how nearly rigid EF-G rectifies inherent and spontaneous ribosomal dynamics into tRNA-mRNA translocation, whereas GTP hydrolysis and Pi release drive EF-G dissociation.
Genomic analyses provide insights into spinach domestication and the genetic basis of agronomic traits
Authors: Cai Xiaofeng , Sun Xuepeng , Xu Chenxi , Sun Honghe , Wang Xiaoli , Ge Chenhui , Zhang Zhonghua , Wang Quanxi , Fei Zhangjun , Jiao Chen , Wang Quanhua 
Published: December 2021

AbstractSpinach is a nutritious leafy vegetable belonging to the family Chenopodiaceae. Here we report a high-quality chromosome-scale reference genome assembly of spinach and genome resequencing of 305 cultivated and wild spinach accessions. Reconstruction of ancestral Chenopodiaceae karyotype indicates substantial genome rearrangements in spinach after its divergence from ancestral Chenopodiaceae, coinciding with high repeat content in the spinach genome. Population genomic analyses provide insights into spinach genetic diversity and population differentiation. Genome-wide association studies of 20 agronomical traits identify numerous significantly associated regions and candidate genes for these traits. Domestication sweeps in the spinach genome are identified, some of which are associated with important traits (e.g., leaf phenotype, bolting and flowering), demonstrating the role of artificial selection in shaping spinach phenotypic evolution. This study provides not only insights into the spinach evolution and domestication but also valuable resources for facilitating spinach breeding.
Clonal architecture predicts clinical outcomes and drug sensitivity in acute myeloid leukemia
Authors: Benard Brooks A. , Leak Logan B. , Azizi Armon , Thomas Daniel , Gentles Andrew J. , Majeti Ravindra 
Published: December 2021

AbstractThe impact of clonal heterogeneity on disease behavior or drug response in acute myeloid leukemia remains poorly understood. Using a cohort of 2,829 patients, we identify features of clonality associated with clinical features and drug sensitivities. High variant allele frequency for 7 mutations (including NRAS and TET2) associate with dismal prognosis; elevated GATA2 variant allele frequency correlates with better outcomes. Clinical features such as white blood cell count and blast percentage correlate with the subclonal abundance of mutations such as TP53 and IDH1. Furthermore, patients with cohesin mutations occurring before NPM1, or transcription factor mutations occurring before splicing factor mutations, show shorter survival. Surprisingly, a branched pattern of clonal evolution is associated with superior clinical outcomes. Finally, several mutations (including NRAS and IDH1) predict drug sensitivity based on their subclonal abundance. Together, these results demonstrate the importance of assessing clonal heterogeneity with implications for prognosis and actionable biomarkers for therapy.
Seismic reflections from a lithospheric suture zone below the Archaean Yilgarn Craton
Authors: Calvert Andrew J. , Doublier Michael P. , Sellars Samantha E. 
Published: December 2021

AbstractSeismic reflectors in the uppermost mantle, which can indicate past plate tectonic subduction, are exceedingly rare below Archaean cratons, and restricted to the Neoarchaean. Here we present reprocessed seismic reflection profiles from the northwest Archaean Yilgarn Craton and the Palaeoproterozoic Capricorn Orogen of western Australia that reveal the existence of a ~4 km thick south-dipping band of seismic reflectors that extends from the base of the Archaean crust to at least 60 km depth. We interpret these reflectors, which lie south of a ~50 km deep crustal root, as a relict suture zone within the lithosphere. We suggest that the mantle reflectors were created either by subduction of an oceanic plate along the northern edge of the Yilgarn Craton, which started in the Mesoarchaean and produced the rocks in northern Yilgarn greenstone belts that formed in a supra-subduction zone setting, or, alternatively, by underthrusting of continental crust deep into the lithosphere during the Palaeoproterozoic.
Global cooling induced by biophysical effects of bioenergy crop cultivation
Authors: Wang Jingmeng , Li Wei , Ciais Philippe , Li Laurent Z. X. , Chang Jinfeng , Goll Daniel , Gasser Thomas , Huang Xiaomeng , Devaraju Narayanappa , Boucher Olivier 
Published: December 2021

AbstractBioenergy crop with carbon capture and storage (BECCS) is a key negative emission technology to meet carbon neutrality. However, the biophysical effects of widespread bioenergy crop cultivation on temperature remain unclear. Here, using a coupled atmosphere-land model with an explicit representation of lignocellulosic bioenergy crops, we find that after 50 years of large-scale bioenergy crop cultivation following plausible scenarios, global air temperature decreases by 0.03~0.08 °C, with strong regional contrasts and interannual variability. Over the cultivated regions, woody crops induce stronger cooling effects than herbaceous crops due to larger evapotranspiration rates and smaller aerodynamic resistance. At the continental scale, air temperature changes are not linearly proportional to the cultivation area. Sensitivity tests show that the temperature change is robust for eucalypt but more uncertain for switchgrass among different cultivation maps. Our study calls for new metrics to take the biophysical effects into account when assessing the climate mitigation capacity of BECCS.
Convergent morphology and divergent phenology promote the coexistence of Morpho butterfly species
Authors: Le Roy Camille , Roux Camille , Authier Elisabeth , Parrinello Hugues , Bastide Héloïse , Debat Vincent , Llaurens Violaine 
Published: December 2021

AbstractThe coexistence of closely-related species in sympatry is puzzling because ecological niche proximity imposes strong competition and reproductive interference. A striking example is the widespread wing pattern convergence of several blue-bandedMorphobutterfly species with overlapping ranges of distribution. Here we perform a series of field experiments using flyingMorphodummies placed in a natural habitat. We show that similarity in wing colour pattern indeed leads to interspecific territoriality and courtship among sympatric species. In spite of such behavioural interference, demographic inference from genomic data shows that sympatric closely-relatedMorphospecies are genetically isolated. Mark-recapture experiments in the two most closely-related species unravel a strong temporal segregation in patrolling activity of males. Such divergence in phenology reduces the costs of reproductive interference while simultaneously preserving the benefits of convergence in non-reproductive traits in response to common ecological pressures. Henceforth, the evolution of multiple traits may favour species diversification in sympatry by partitioning niche in different dimensions.
Fano interference in quantum resonances from angle-resolved elastic scattering
Authors: Paliwal Prerna , Blech Alexander , Koch Christiane P. , Narevicius Edvardas 
Published: December 2021

AbstractAsymmetric spectral line shapes are a hallmark of interference of a quasi-bound state with a continuum of states. Such line shapes are well known for multichannel systems, for example, in photoionization or Feshbach resonances in molecular scattering. On the other hand, in resonant single channel scattering, the signature of such interference may disappear due to the orthogonality of partial waves. Here, we show that probing the angular dependence of the cross section allows us to unveil asymmetric Fano profiles also in a single channel shape resonance. We observe a shift in the peak of the resonance profile in the elastic collisions between metastable helium and deuterium molecules with detection angle, in excellent agreement with theoretical predictions from full quantum scattering calculations. Using a model description for the partial wave interference, we can disentangle the resonant and background contributions and extract the relative phase responsible for the characteristic Fano-like profiles from our experimental measurements.
Comparative quantification of local climate regulation by green and blue urban areas in cities across Europe
Authors: Goldenberg Romain , Kalantari Zahra , Destouni Georgia 
Published: December 2021

AbstractUrban growth alters environmental conditions with major consequences for climate regulation and the exposure of population to heat. Nature-based solutions may be used to alleviate the increasing urban climate pressures, but the climate regulation services that these solutions can supply for and across different urban conditions remains understudied. We comparatively investigate the urban ecosystem service realization (considering the ecosystem service supply and demand spatial interactions) of local climate regulation by vegetated (green) and water-covered (blue) areas across 660 European cities. Results show relatively robust power-law relationships with city population density (average R2 of 0.34) of main indicators of ecosystem service realization. Country-wise fitting for city-average indicators strengthens these relationships, in particular for western European cities (average R2 of 0.66). Cross-city results also show strong power-law relationship of effectiveness in ecosystem service realization with socio-economic measures like Human Development Index and GPD per capita, in particular for the area fraction of city parts with high ecosystem service realization (R2 of 0.77). The quantified relationships are useful for comparative understanding of differences in ecosystem services realization between cities and city parts, and quantitative projection of possible change trends under different types of city growth so that relevant measures can be taken to counteract undesirable trends.
Cloaking, trapping and superlensing of lamb waves with negative refraction
Authors: Legrand François , Gérardin Benoît , Bruno François , Laurent Jérôme , Lemoult Fabrice , Prada Claire , Aubry Alexandre 
Published: December 2021

AbstractWe report on experimental and numerical implementations of devices based on the negative refraction of elastic guided waves, the so-called Lamb waves. Consisting in plates of varying thickness, these devices rely on the concept of complementary media, where a particular layout of negative index media can cloak an object with its anti-object or trap waves around a negative corner. The diffraction cancellation operated by negative refraction is investigated by means of laser ultrasound experiments. However, unlike original theoretical predictions, these intriguing wave phenomena remain, nevertheless, limited to the propagating component of the wave-field. To go beyond the diffraction limit, negative refraction is combined with the concept of metalens, a device converting the evanescent components of an object into propagating waves. The transport of an evanescent wave-field is then possible from an object plane to a far-field imaging plane. Twenty years after Pendry’s initial proposal, this work thus paves the way towards an elastic superlens.
Genetic determinants of liking and intake of coffee and other bitter foods and beverages
Authors: Cornelis Marilyn C. , van Dam Rob M. 
Published: December 2021

AbstractCoffee is a widely consumed beverage that is naturally bitter and contains caffeine. Genome-wide association studies (GWAS) of coffee drinking have identified genetic variants involved in caffeine-related pathways but not in taste perception. The taste of coffee can be altered by addition of milk/sweetener, which has not been accounted for in GWAS. Using UK and US cohorts, we test the hypotheses that genetic variants related to taste are more strongly associated with consumption of black coffee than with consumption of coffee with milk or sweetener and that genetic variants related to caffeine pathways are not differentially associated with the type of coffee consumed independent of caffeine content. Contrary to our hypotheses, genetically inferred caffeine sensitivity was more strongly associated with coffee taste preferences than with genetically inferred bitter taste perception. These findings extended to tea and dark chocolate. Taste preferences and physiological caffeine effects intertwine in a way that is difficult to distinguish for individuals which may represent conditioned taste preferences.
Distinct trans-placental effects of maternal immune activation by TLR3 and TLR7 agonists: implications for schizophrenia risk
Authors: Kwon Jaedeok , Suessmilch Maria , McColl Alison , Cavanagh Jonathan , Morris Brian J. 
Published: December 2021

AbstractExposure to infection in utero predisposes towards psychiatric diseases such as autism, depression and schizophrenia in later life. The mechanisms involved are typically studied by administering mimetics of double-stranded (ds) virus or bacterial infection to pregnant rats or mice. The effect of single-stranded (ss) virus mimetics has been largely ignored, despite evidence linking prenatal ss virus exposure with psychiatric disease. Understanding the effects of gestational ss virus exposure has become even more important with recent events. In this study, in pregnant mice, we compare directly the effects, on the maternal blood, placenta and the embryonic brain, of maternal administration of ds-virus mimetic poly I:C (to activate Toll-like receptor 3, TLR3) and ss-virus mimetic resiquimod (to activate TLR7/8). We find that, 4 h after the administration, both poly I:C and resiquimod elevated the levels of IL-6, TNFα, and chemokines including CCL2 and CCL5, in maternal plasma. Both agents also increased placental mRNA levels of IL-6 and IL-10, but only resiquimod increased placental TNFα mRNA. In foetal brain, poly I:C produced no detectable immune-response-related increases, whereas pronounced increases in cytokine (e.g.Il-6,Tnfα) and chemokine (e.g.Ccl2,Ccl5) expression were observed with maternal resiquimod administration. The data show substantial differences between the effect of maternal exposure to a TLR7/8 activator as compared to a TLR3 activator. There are significant implications for future modelling of diseases where maternal ss virus exposure contributes to environmental disease risk in offspring.
Spatiotemporal variations of agricultural water footprint and its economic benefits in Xinjiang, northwestern China
Authors: Li Yinbo , Deng Mingjiang 
Published: December 2021

AbstractAgriculture is the largest water user and is the main driving force behind water stress in Xinjiang, northwestern China. In this study, the water footprint (WF) (blue, green and gray WF) of main crop production and their temporal and spatial characteristics in Xinjiang were estimated in 2006, 2010, 2014 and 2018. The blue water footprint deficit (BWFd) was conducted and food productivity and economic benefits of WF were also analyzed via the water consumption per output value (food productivity and economic benefits). The results reveal that the WF increased from 22.75 to 44.16 billion m3 during 2006–2018 in Xinjiang, of which cotton, corn and wheat are main contributors of WF. In terms of different regions, corn has the largest WF in north Xinjiang and cotton has the largest WF in south and east Xinjiang. The BWFd broadened from − 11.51 to + 13.26 billion m3 in Xinjiang with the largest increased BWFd in Kashgar (from − 3.35 to 1.40 billion m3) and Aksu (from − 2.92 to 2.23 billion m3) of south Xinjiang and in Shihezi (from − 0.11 to 2.90 billion m3) of north Xinjiang. In addition, the water footprint food productivity does not well correspond with the water footprint economic benefits in prefectures of Xinjiang. It means we should consider the food yields priority and economic benefits priority to formulate a scientific and effective supervisor mode to realize the sustainable management of agricultural water in prefectures of Xinjiang.
Independent evaluation of 12 artificial intelligence solutions for the detection of tuberculosis
Authors: Codlin Andrew J. , Dao Thang Phuoc , Vo Luan Nguyen Quang , Forse Rachel J. , Van Truong Vinh , Dang Ha Minh , Nguyen Lan Huu , Nguyen Hoa Binh , Nguyen Nhung Viet , Sidney-Annerstedt Kristi , Squire Bertie , Lönnroth Knut , Caws Maxine 
Published: December 2021

AbstractThere have been few independent evaluations of computer-aided detection (CAD) software for tuberculosis (TB) screening, despite the rapidly expanding array of available CAD solutions. We developed a test library of chest X-ray (CXR) images which was blindly re-read by two TB clinicians with different levels of experience and then processed by 12 CAD software solutions. Using Xpert MTB/RIF results as the reference standard, we compared the performance characteristics of each CAD software against both an Expert and Intermediate Reader, using cut-off thresholds which were selected to match the sensitivity of each human reader. Six CAD systems performed on par with the Expert Reader (Qure.ai, DeepTek, Delft Imaging, JF Healthcare, OXIPIT, and Lunit) and one additional software (Infervision) performed on par with the Intermediate Reader only. Qure.ai, Delft Imaging and Lunit were the only software to perform significantly better than the Intermediate Reader. The majority of these CAD software showed significantly lower performance among participants with a past history of TB. The radiography equipment used to capture the CXR image was also shown to affect performance for some CAD software. TB program implementers now have a wide selection of quality CAD software solutions to utilize in their CXR screening initiatives.
Spatial and temporal multiplet analysis for identification of dominant fluid migration path at The Geysers geothermal field, California
Authors: Staszek M. , Rudziński Ł. , Kwiatek G. 
Published: December 2021

AbstractMultiplet analysis is based on the identification of seismic events with very similar waveforms which are used then to enhance seismological analysis e.g. by precise relocation of sources. In underground fluid injection conditions, it is a tool frequently used for imaging of subsurface fracture system. We identify over 150 repeatedly activated seismic sources within seismicity cluster induced by fluid injection in NW part of The Geysers geothermal field (California). Majority of multiple events (ME) occur along N–S oriented planar structure which we interpret as a fault plane. Remaining ME are distributed along structures interpreted as fractures, forming together a system of interconnected cracks enabling fluid migration. Temporal analysis reveals that during periods of relatively low fluid injection the proportion of ME to non-multiple events is higher than during periods of high injection. Moreover, ME which occur within the fault differ in activity rate and source properties from ME designating the fractures and non-multiple events. In this study we utilize observed differences between ME occurring within various structures and non-multiple events to describe hydraulic conditions within the reservoir. We show that spatial and temporal analysis of multiplets can be used for identification and characterization of dominant fluid migration paths.