bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating multiple genomic technologies to investigate an outbreak of carbapenemase-producing Enterobacter hormaechei
Authors: Roberts Leah W. , Harris Patrick N. A. , Forde Brian M. , Ben Zakour Nouri L. , Catchpoole Elizabeth , Stanton-Cook Mitchell , Phan Minh-Duy , Sidjabat Hanna E. , Bergh Haakon , Heney Claire , Gawthorne Jayde A. , Lipman Jeffrey , Allworth Anthony , Chan Kok-Gan , Chong Teik Min , Yin Wai-Fong , Schembri Mark A. , Paterson David L. , Beatson Scott A. 
Published: January 2020

AbstractCarbapenem-resistant Enterobacteriaceae (CRE) represent an urgent threat to human health. Here we report the application of several complementary whole-genome sequencing (WGS) technologies to characterise a hospital outbreak of blaIMP-4 carbapenemase-producing E. hormaechei. Using Illumina sequencing, we determined that all outbreak strains were sequence type 90 (ST90) and near-identical. Comparison to publicly available data linked all outbreak isolates to a 2013 isolate from the same ward, suggesting an environmental source in the hospital. Using Pacific Biosciences sequencing, we resolved the complete context of the blaIMP-4 gene on a large IncHI2 plasmid carried by all IMP-4-producing strains across different hospitals. Shotgun metagenomic sequencing of environmental samples also found evidence of ST90 E. hormaechei and the IncHI2 plasmid within the hospital plumbing. Finally, Oxford Nanopore sequencing rapidly resolved the true relationship of subsequent isolates to the initial outbreak. Overall, our strategic application of three WGS technologies provided an in-depth analysis of the outbreak.
PTH induces bone loss via microbial-dependent expansion of intestinal TNF+ T cells and Th17 cells
Authors: Yu Mingcan , Malik Tyagi Abdul , Li Jau-Yi , Adams Jonathan , Denning Timothy L. , Weitzmann M. Neale , Jones Rheinallt M. , Pacifici Roberto 
Published: January 2020

AbstractBone loss is a frequent but not universal complication of hyperparathyroidism. Using antibiotic-treated or germ-free mice, we show that parathyroid hormone (PTH) only caused bone loss in mice whose microbiota was enriched by the Th17 cell-inducing taxa segmented filamentous bacteria (SFB). SFB+microbiota enabled PTH to expand intestinal TNF+T and Th17 cells and increase their S1P-receptor-1 mediated egress from the intestine and recruitment to the bone marrow (BM) that causes bone loss. CXCR3-mediated TNF+T cell homing to the BM upregulated the Th17 chemoattractant CCL20, which recruited Th17 cells to the BM. This study reveals mechanisms for microbiota-mediated gut–bone crosstalk in mice models of hyperparathyroidism that may help predict its clinical course. Targeting the gut microbiota or T cell migration may represent therapeutic strategies for hyperparathyroidism.
Dstyk mutation leads to congenital scoliosis-like vertebral malformations in zebrafish via dysregulated mTORC1/TFEB pathway
Authors: Sun Xianding , Zhou Yang , Zhang Ruobin , Wang Zuqiang , Xu Meng , Zhang Dali , Huang Junlan , Luo Fengtao , Li Fangfang , Ni Zhenhong , Zhou Siru , Chen Hangang , Chen Shuai , Chen Liang , Du Xiaolan , Chen Bo , Huang Haiyang , Liu Peng , Yin Liangjun , Qiu Juhui , Chen Di , Deng Chuxia , Xie Yangli , Luo Lingfei , Chen Lin 
Published: January 2020

AbstractCongenital scoliosis (CS) is a complex genetic disorder characterized by vertebral malformations. The precise etiology of CS is not fully defined. Here, we identify that mutation in dual serine/threonine and tyrosine protein kinase (dstyk) lead to CS-like vertebral malformations in zebrafish. We demonstrate that the scoliosis in dstyk mutants is related to the wavy and malformed notochord sheath formation and abnormal axial skeleton segmentation due to dysregulated biogenesis of notochord vacuoles and notochord function. Further studies show that DSTYK is located in late endosomal/lysosomal compartments and is involved in the lysosome biogenesis in mammalian cells. Dstyk knockdown inhibits notochord vacuole and lysosome biogenesis through mTORC1-dependent repression of TFEB nuclear translocation. Inhibition of mTORC1 activity can rescue the defect in notochord vacuole biogenesis and scoliosis in dstyk mutants. Together, our findings reveal a key role of DSTYK in notochord vacuole biogenesis, notochord morphogenesis and spine development through mTORC1/TFEB pathway.
Kindlin-2 modulates MafA and β-catenin expression to regulate β-cell function and mass in mice
Authors: Zhu Ke , Lai Yumei , Cao Huiling , Bai Xiaochun , Liu Chuanju , Yan Qinnan , Ma Liting , Chen Di , Kanaporis Giedrius , Wang Junqi , Li Luyuan , Cheng Tao , Wang Yong , Wu Chuanyue , Xiao Guozhi 
Published: January 2020

Abstractβ-Cell dysfunction and reduction in β-cell mass are hallmark events of diabetes mellitus. Here we show that β-cells express abundant Kindlin-2 and deleting its expression causes severe diabetes-like phenotypes without markedly causing peripheral insulin resistance. Kindlin-2, through its C-terminal region, binds to and stabilizes MafA, which activates insulin expression. Kindlin-2 loss impairs insulin secretion in primary human and mouse islets in vitro and in mice by reducing, at least in part, Ca2+ release in β-cells. Kindlin-2 loss activates GSK-3β and downregulates β-catenin, leading to reduced β-cell proliferation and mass. Kindlin-2 loss reduces the percentage of β-cells and concomitantly increases that of α-cells during early pancreatic development. Genetic activation of β-catenin in β-cells restores the diabetes-like phenotypes induced by Kindlin-2 loss. Finally, the inducible deletion of β-cell Kindlin-2 causes diabetic phenotypes in adult mice. Collectively, our results establish an important function of Kindlin-2 and provide a potential therapeutic target for diabetes.
Disruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements
Authors: Henderson Rory , Lu Maolin , Zhou Ye , Mu Zekun , Parks Robert , Han Qifeng , Hsu Allen L. , Carter Elizabeth , Blanchard Scott C. , Edwards R J , Wiehe Kevin , Saunders Kevin O. , Borgnia Mario J. , Bartesaghi Alberto , Mothes Walther , Haynes Barton F. , Acharya Priyamvada , Munir Alam S. 
Published: January 2020

AbstractThe trimeric HIV-1 Envelope protein (Env) mediates viral-host cell fusion via a network of conformational transitions, with allosteric elements in each protomer orchestrating host receptor-induced exposure of the co-receptor binding site and fusion elements. To understand the molecular details of this allostery, here, we introduce Env mutations aimed to prevent CD4-induced rearrangements in the HIV-1 BG505 Env trimer. Binding analysis and single−molecule Förster Resonance Energy Transfer confirm that these mutations prevent CD4-induced transitions of the HIV-1 Env. Structural analysis by single−particle cryo-electron microscopy performed on the BG505 SOSIP mutant Env proteins shows rearrangements in the gp120 topological layer contacts with gp41. Displacement of a conserved tryptophan (W571) from its typical pocket in these Env mutants renders the Env insensitive to CD4 binding. These results reveal the critical function of W571 as a conformational switch in Env allostery and receptor-mediated viral entry and provide insights on Env conformation that are relevant for vaccine design.
High-quality genome sequence of white lupin provides insight into soil exploration and seed quality
Authors: Hufnagel Bárbara , Marques André , Soriano Alexandre , Marquès Laurence , Divol Fanchon , Doumas Patrick , Sallet Erika , Mancinotti Davide , Carrere Sébastien , Marande William , Arribat Sandrine , Keller Jean , Huneau Cécile , Blein Thomas , Aimé Delphine , Laguerre Malika , Taylor Jemma , Schubert Veit , Nelson Matthew , Geu-Flores Fernando , Crespi Martin , Gallardo Karine , Delaux Pierre-Marc , Salse Jérôme , Bergès Hélène , Guyot Romain , Gouzy Jérôme , Péret Benjamin 
Published: January 2020

AbstractWhite lupin (Lupinus albus L.) is an annual crop cultivated for its protein-rich seeds. It is adapted to poor soils due to the production of cluster roots, which are made of dozens of determinate lateral roots that drastically improve soil exploration and nutrient acquisition (mostly phosphate). Using long-read sequencing technologies, we provide a high-quality genome sequence of a cultivated accession of white lupin (2n = 50, 451 Mb), as well as de novo assemblies of a landrace and a wild relative. We describe a modern accession displaying increased soil exploration capacity through early establishment of lateral and cluster roots. We also show how seed quality may have been impacted by domestication in term of protein profiles and alkaloid content. The availability of a high-quality genome assembly together with companion genomic and transcriptomic resources will enable the development of modern breeding strategies to increase and stabilize white lupin yield.
Dispersion fields reveal the compositional structure of South American vertebrate assemblages
Authors: Borregaard Michael K. , Graves Gary R. , Rahbek Carsten 
Published: January 2020

AbstractThe causes of continental patterns in species richness continue to spur heated discussion. Hypotheses based on ambient energy have dominated the debate, but are increasingly being challenged by hypotheses that model richness as the overlap of species ranges, ultimately controlled by continental range dynamics of individual species. At the heart of this controversy lies the question of whether species richness of individual grid cells is controlled by local factors, or reflects larger-scale spatial patterns in the turnover of species’ ranges. Here, we develop a new approach based on assemblage dispersion fields, formed by overlaying the geographic ranges of all species co-occurring in a grid cell. We created dispersion fields for all tetrapods of South America, and characterized the orientation and shape of dispersion fields as a vector field. The resulting maps demonstrate the existence of macro-structures in the turnover of biotic similarity at continental scale that are congruent among vertebrate classes. These structures underline the importance of continental-scale processes for species richness in individual assemblages.
Nr4a1 suppresses cocaine-induced behavior via epigenetic regulation of homeostatic target genes
Authors: Carpenter Marco D. , Hu Qiwen , Bond Allison M. , Lombroso Sonia I. , Czarnecki Kyle S. , Lim Carissa J. , Song Hongjun , Wimmer Mathieu E. , Pierce R. Christopher , Heller Elizabeth A. 
Published: January 2020

AbstractEndogenous homeostatic mechanisms can restore normal neuronal function following cocaine-induced neuroadaptations. Such mechanisms may be exploited to develop novel therapies for cocaine addiction, but a molecular target has not yet been identified. Here we profiled mouse gene expression during early and late cocaine abstinence to identify putative regulators of neural homeostasis. Cocaine activated the transcription factor, Nr4a1, and its target gene, Cartpt, a key molecule involved in dopamine metabolism. Sustained activation of Cartpt at late abstinence was coupled with depletion of the repressive histone modification, H3K27me3, and enrichment of activating marks, H3K27ac and H3K4me3. Using both CRISPR-mediated and small molecule Nr4a1 activation, we demonstrated the direct causal role of Nr4a1 in sustained activation of Cartpt and in attenuation of cocaine-evoked behavior. Our findings provide evidence that targeting abstinence-induced homeostatic gene expression is a potential therapeutic target in cocaine addiction.
Biomacromolecules enabled dendrite-free lithium metal battery and its origin revealed by cryo-electron microscopy
Authors: Ju Zhijin , Nai Jianwei , Wang Yao , Liu Tiefeng , Zheng Jianhui , Yuan Huadong , Sheng Ouwei , Jin Chengbin , Zhang Wenkui , Jin Zhong , Tian He , Liu Yujing , Tao Xinyong 
Published: January 2020

AbstractMetallic lithium anodes are highly promising for revolutionizing current rechargeable batteries because of their ultrahigh energy density. However, the application of lithium metal batteries is considerably impeded by lithium dendrite growth. Here, a biomacromolecule matrix obtained from the natural membrane of eggshell is introduced to control lithium growth and the mechanism is motivated by how living organisms regulate the orientation of inorganic crystals in biomineralization. Specifically, cryo-electron microscopy is utilized to probe the structure of lithium at the atomic level. The dendrites growing along the preferred < 111 > crystallographic orientation are greatly suppressed in the presence of the biomacromolecule. Furthermore, the naturally soluble chemical species in the biomacromolecules can participate in the formation of solid electrolyte interphase upon cycling, thus effectively homogenizing the lithium deposition. The lithium anodes employing bioinspired design exhibit enhanced cycling capability. This work sheds light on identifying substantial challenges in lithium anodes for developing advanced batteries.
Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing
Authors: Li Kailong , Liu Yuxuan , Cao Hui , Zhang Yuannyu , Gu Zhimin , Liu Xin , Yu Andy , Kaphle Pranita , Dickerson Kathryn E. , Ni Min , Xu Jian 
Published: January 2020

AbstractTissue-specific gene expression requires coordinated control of gene-proximal and -distal cis-regulatory elements (CREs), yet functional analysis of gene-distal CREs such as enhancers remains challenging. Here we describe CRISPR/dCas9-based enhancer-targeting epigenetic editing systems, enCRISPRa and enCRISPRi, for efficient analysis of enhancer function in situ and in vivo. Using dual effectors capable of re-writing enhancer-associated chromatin modifications, we show that enCRISPRa and enCRISPRi modulate gene transcription by remodeling local epigenetic landscapes at sgRNA-targeted enhancers and associated genes. Comparing with existing methods, the improved systems display more robust perturbations of enhancer activity and gene transcription with minimal off-targets. Allele-specific targeting of enCRISPRa to oncogenic TAL1 super-enhancer modulates TAL1 expression and cancer progression in xenotransplants. Single or multi-loci perturbations of lineage-specific enhancers using an enCRISPRi knock-in mouse establish in vivo evidence for lineage-restricted essentiality of developmental enhancers during hematopoiesis. Hence, enhancer-targeting CRISPR epigenetic editing provides opportunities for interrogating enhancer function in native biological contexts.
Large lattice distortions and size-dependent bandgap modulation in epitaxial halide perovskite nanowires
Authors: Oksenberg Eitan , Merdasa Aboma , Houben Lothar , Kaplan-Ashiri Ifat , Rothman Amnon , Scheblykin Ivan G. , Unger Eva L. , Joselevich Ernesto 
Published: January 2020

AbstractMetal-halide perovskites have been shown to be remarkable and promising optoelectronic materials. However, despite ongoing research from multiple perspectives, some fundamental questions regarding their optoelectronic properties remain controversial. One reason is the high-variance of data collected from, often unstable, polycrystalline thin films. Here we use ordered arrays of stable, single-crystal cesium lead bromide (CsPbBr3) nanowires grown by surface-guided chemical vapor deposition to study fundamental properties of these semiconductors in a one-dimensional model system. Specifically, we uncover the origin of an unusually large size-dependent luminescence emission spectral blue-shift. Using multiple spatially resolved spectroscopy techniques, we establish that bandgap modulation causes the emission shift, and by correlation with state-of-the-art electron microscopy methods, we reveal its origin in substantial and uniform lattice rotations due to heteroepitaxial strain and lattice relaxation. Understanding strain and its effect on the optoelectronic properties of these dynamic materials, from the atomic scale up, is essential to evaluate their performance limits and fundamentals of charge carrier dynamics.
Changes in left ventricular blood flow during diastole due to differences in chamber size in healthy dogs
Authors: Matsuura Katsuhiro , Sato Kotomi , Shimada Kazumi , Goya Seijirow , Uemura Akiko , Iso Takeshi , Yazaki Kana , Yilmaz Zeki , Takahashi Ken , Tanaka Ryou 
Published: January 2020

AbstractVorticity is a novel index that reflects diastolic function of left ventricle. The size of the ventricle can influence the ventricular diastolic blood flow. We evaluated effect of ventricular size on diastolic function and diastolic intracardiac blood flow using a particular species of dogs, which has a wide range of body size. Vector flow mapping was used for evaluation of intracardiac blood flow, and intraventricular pressure gradient (IVPG) was used for evaluation of diastolic function. 58 dogs weighing 1.3–42.3 kg were included in this study. Vorticity was found to be inversely proportional to the length of the ventricular chamber. Intraventricular pressure difference was positively correlated with the length of the left ventricle, whereas IVPG was not. This study showed that the vorticity is influenced by the size of the left ventricle independently of other factors. To evaluate the hemodynamic state of each individual appropriately by using vorticity and IVPD, ventricular size should be taken into account especially in the field of veterinary medicine and human pediatric and adolescent cardiology.
The Technome - A Predictive Internal Calibration Approach for Quantitative Imaging Biomarker Research
Authors: Mühlberg Alexander , Katzmann Alexander , Heinemann Volker , Kärgel Rainer , Wels Michael , Taubmann Oliver , Lades Félix , Huber Thomas , Maurus Stefan , Holch Julian , Faivre Jean-Baptiste , Sühling Michael , Nörenberg Dominik , Rémy-Jardin Martine 
Published: January 2020

AbstractThe goal of radiomics is to convert medical images into a minable data space by extraction of quantitative imaging features for clinically relevant analyses, e.g. survival time prediction of a patient. One problem of radiomics from computed tomography is the impact of technical variation such as reconstruction kernel variation within a study. Additionally, what is often neglected is the impact of inter-patient technical variation, resulting from patient characteristics, even when scan and reconstruction parameters are constant. In our approach, measurements within 3D regions-of-interests (ROI) are calibrated by further ROIs such as air, adipose tissue, liver, etc. that are used as control regions (CR). Our goal is to derive general rules for an automated internal calibration that enhance prediction, based on the analysed features and a set of CRs. We define qualification criteria motivated by status-quo radiomics stability analysis techniques to only collect information from the CRs which is relevant given a respective task. These criteria are used in an optimisation to automatically derive a suitable internal calibration for prediction tasks based on the CRs. Our calibration enhanced the performance for centrilobular emphysema prediction in a COPD study and prediction of patients’ one-year-survival in an oncological study.
Multi-aged social behaviour based on artiodactyl tracks in an early Miocene palustrine wetland (Ebro Basin, Spain)
Authors: Díaz-Martínez Ignacio , Suarez-Hernando Oier , Larrasoaña Juan Cruz , Martínez-García Blanca María , Baceta Juan Ignacio , Murelaga Xabier 
Published: January 2020

AbstractWe present a new locality with at least 880 vertebrate tracks found at the top of a limestone bed from the lower Miocene Tudela Formation (Spain). The trampled surface was formed by artiodactyls that crossed a muddy carbonate accumulated under the influence of water level variations in a palustrine environment. The tracks reflect different types of morphological preservation. The well-preserved tracks have tetradactyl digit impressions caused by both manus and pes, and are the type series of a new artiodactyl ichnotaxon,Fustinianapodus arriazuiichnogen. nov. and ichnosp. nov. The rest of the tracks, which are not as well preserved, are didactyl and were classified as undetermined artiodactyl tracks. According to their preservation, morphology, size, arrangement and orientation, we propose that this tracksite is the product of a social behaviour, particularly gregariousness, of a multi-age group of artiodactyls ~19 Ma ago. The morphologic and palaeoecologic data presented here suggest that the trackmakers were a group of anthracotheres with a livelihood similar to current hippos. They crossed, periodically, a fresh water palustrine area along some preferential pathways (trails).
The association between mineralised tissue formation and the mechanical local in vivo environment: Time-lapsed quantification of a mouse defect healing model
Authors: Tourolle né Betts Duncan C. , Wehrle Esther , Paul Graeme R. , Kuhn Gisela A. , Christen Patrik , Hofmann Sandra , Müller Ralph 
Published: January 2020

AbstractAn improved understanding of how local mechanical stimuli guide the fracture healing process has the potential to enhance clinical treatment of bone injury. Recent preclinical studies of bone defect in animal models have used cross-sectional data to examine this phenomenon indirectly. In this study, a direct time-lapsed imaging approach was used to investigate the local mechanical strains that precede the formation of mineralised tissue at the tissue scale. The goal was to test two hypotheses: 1) the local mechanical signal that precedes the onset of tissue mineralisation is higher in areas which mineralise, and 2) this local mechanical signal is independent of the magnitude of global mechanical loading of the tissue in the defect. Two groups of mice with femoral defects of length 0.85 mm (n = 10) and 1.45 mm (n = 9) were studied, allowing for distinct distributions of tissue scale strains in the defects. The regeneration and (re)modelling of mineralised tissue was observed weekly usingin vivomicro-computed tomography (micro-CT), which served as a ground truth for resolving areas of mineralised tissue formation. The mechanical environment was determined using micro-finite element analysis (micro-FE) on baseline images. The formation of mineralised tissue showed strong association with areas of higher mechanical strain (area-under-the-curve: 0.91 ± 0.04, true positive rate: 0.85 ± 0.05) while surface based strains could correctly classify 43% of remodelling events. These findings support our hypotheses by showing a direct association between the local mechanical strains and the formation of mineralised tissue.
Cell release during perfusion reflects cold ischemic injury in rat livers
Authors: de Vries Reinier J. , Pendexter Casie A. , Cronin Stephanie E. J. , Marques Beatriz , Hafiz Ehab O. A. , Muzikansky Alona , van Gulik Thomas M. , Markmann James F. , Stott Shannon L. , Yeh Heidi , Toner Mehmet , Uygun Korkut , Tessier Shannon N. 
Published: January 2020

AbstractThe global shortage of donor organs has made it crucial to deeply understand and better predict donor liver viability. However, biomarkers that effectively assess viability of marginal grafts for organ transplantation are currently lacking. Here, we showed that hepatocytes, sinusoidal endothelial, stellate, and liver-specific immune cells were released into perfusates from Lewis rat livers as a result of cold ischemia and machine perfusion. Perfusate comparison analysis of fresh livers and cold ischemic livers showed that the released cell profiles were significantly altered by the duration of cold ischemia. Our findings show for the first time that parenchymal cells are released from organs under non-proliferative pathological conditions, correlating with the degree of ischemic injury. Thus, perfusate cell profiles could serve as potential biomarkers of graft viability and indicators of specific injury mechanisms during organ handling and transplantation. Further, parenchymal cell release may have applications in other pathological conditions beyond organ transplantation.