bluuebunny/crossref_metadata_2025_split huggingface dataset:
The RNA landscape of the human placenta in health and disease
Authors: Gong Sungsam , Gaccioli Francesca , Dopierala Justyna , Sovio Ulla , Cook Emma , Volders Pieter-Jan , Martens Lennart , Kirk Paul D. W. , Richardson Sylvia , Smith Gordon C. S. , Charnock-Jones D. Stephen 
Published: May 2021

AbstractThe placenta is the interface between mother and fetus and inadequate function contributes to short and long-term ill-health. The placenta is absent from most large-scale RNA-Seq datasets. We therefore analyze long and small RNAs (~101 and 20 million reads per sample respectively) from 302 human placentas, including 94 cases of preeclampsia (PE) and 56 cases of fetal growth restriction (FGR). The placental transcriptome has the seventh lowest complexity of 50 human tissues: 271 genes account for 50% of all reads. We identify multiple circular RNAs and validate 6 of these by Sanger sequencing across the back-splice junction. Using large-scale mass spectrometry datasets, we find strong evidence of peptides produced by translation of two circular RNAs. We also identify novel piRNAs which are clustered on Chr1 and Chr14. PE and FGR are associated with multiple and overlapping differences in mRNA, lincRNA and circRNA but fewer consistent differences in small RNAs. Of the three protein coding genes differentially expressed in both PE and FGR, one encodes a secreted protein FSTL3 (follistatin-like 3). Elevated serum levels of FSTL3 in pregnant women are predictive of subsequent PE and FGR. To aid visualization of our placenta transcriptome data, we develop a web application (https://www.obgyn.cam.ac.uk/placentome/).
Global population structure and genotyping framework for genomic surveillance of the major dysentery pathogen, Shigella sonnei
Authors: Hawkey Jane , Paranagama Kalani , Baker Kate S. , Bengtsson Rebecca J. , Weill François-Xavier , Thomson Nicholas R. , Baker Stephen , Cerdeira Louise , Iqbal Zamin , Hunt Martin , Ingle Danielle J. , Dallman Timothy J. , Jenkins Claire , Williamson Deborah A. , Holt Kathryn E. 
Published: May 2021

AbstractShigella sonnei is the most common agent of shigellosis in high-income countries, and causes a significant disease burden in low- and middle-income countries. Antimicrobial resistance is increasingly common in all settings. Whole genome sequencing (WGS) is increasingly utilised for S. sonnei outbreak investigation and surveillance, but comparison of data between studies and labs is challenging. Here, we present a genomic framework and genotyping scheme for S. sonnei to efficiently identify genotype and resistance determinants from WGS data. The scheme is implemented in the software package Mykrobe and tested on thousands of genomes. Applying this approach to analyse >4,000 S. sonnei isolates sequenced in public health labs in three countries identified several common genotypes associated with increased rates of ciprofloxacin resistance and azithromycin resistance, confirming intercontinental spread of highly-resistant S. sonnei clones and demonstrating the genomic framework can facilitate monitoring the spread of resistant clones, including those that have recently emerged, at local and global scales.
Global land use changes are four times greater than previously estimated
Authors: Winkler Karina , Fuchs Richard , Rounsevell Mark , Herold Martin 
Published: May 2021

AbstractQuantifying the dynamics of land use change is critical in tackling global societal challenges such as food security, climate change, and biodiversity loss. Here we analyse the dynamics of global land use change at an unprecedented spatial resolution by combining multiple open data streams (remote sensing, reconstructions and statistics) to create the HIstoric Land Dynamics Assessment + (HILDA +). We estimate that land use change has affected almost a third (32%) of the global land area in just six decades (1960-2019) and, thus, is around four times greater in extent than previously estimated from long-term land change assessments. We also identify geographically diverging land use change processes, with afforestation and cropland abandonment in the Global North and deforestation and agricultural expansion in the South. Here, we show that observed phases of accelerating (~1960–2005) and decelerating (2006–2019) land use change can be explained by the effects of global trade on agricultural production.
Dual vaccination against IL-4 and IL-13 protects against chronic allergic asthma in mice
Authors: Conde Eva , Bertrand Romain , Balbino Bianca , Bonnefoy Jonathan , Stackowicz Julien , Caillot Noémie , Colaone Fabien , Hamdi Samir , Houmadi Raïssa , Loste Alexia , Kamphuis Jasper B. J. , Huetz François , Guilleminault Laurent , Gaudenzio Nicolas , Mougel Aurélie , Hardy David , Snouwaert John N. , Koller Beverly H. , Serra Vincent , Bruhns Pierre , Grouard-Vogel Géraldine , Reber Laurent L. 
Published: May 2021

AbstractAllergic asthma is characterized by elevated levels of IgE antibodies, type 2 cytokines such as interleukin-4 (IL-4) and IL-13, airway hyperresponsiveness (AHR), mucus hypersecretion and eosinophilia. Approved therapeutic monoclonal antibodies targeting IgE or IL-4/IL-13 reduce asthma symptoms but require costly lifelong administrations. Here, we develop conjugate vaccines against mouse IL-4 and IL-13, and demonstrate their prophylactic and therapeutic efficacy in reducing IgE levels, AHR, eosinophilia and mucus production in mouse models of asthma analyzed up to 15 weeks after initial vaccination. More importantly, we also test similar vaccines specific for human IL-4/IL-13 in mice expressing human IL-4/IL-13 and the related receptor, IL-4Rα, to find efficient neutralization of both cytokines and reduced IgE levels for at least 11 weeks post-vaccination. Our results imply that dual IL-4/IL-13 vaccination may represent a cost-effective, long-term therapeutic strategy for the treatment of allergic asthma as demonstrated in mouse models, although additional studies are warranted to assess its safety and feasibility.
Protecting local water quality has global benefits
Authors: Downing John A. , Polasky Stephen , Olmstead Sheila M. , Newbold Stephen C. 
Published: May 2021

AbstractSurface water is among Earth’s most important resources. Yet, benefit–cost studies often report that the costs of water quality protection exceed its benefits. One possible reason for this seeming paradox is that often only a narrow range of local water quality benefits are considered. In particular, the climate damages from water pollution have rarely been quantified. Recent advances in global water science allow the computation of the global methane emission from lakes caused by human nutrient enrichment (eutrophication). Here, we estimate the present value of the global social cost of eutrophication-driven methane emissions from lakes between 2015 and 2050 to be $7.5–$81 trillion (2015 $US), and in a case-study for one well-studied lake (Lake Erie) we find the global value of avoiding eutrophication exceeds local values of either beach use or sport fishing by 10-fold.
Variability of plasmid fitness effects contributes to plasmid persistence in bacterial communities
Authors: Alonso-del Valle Aida , León-Sampedro Ricardo , Rodríguez-Beltrán Jerónimo , DelaFuente Javier , Hernández-García Marta , Ruiz-Garbajosa Patricia , Cantón Rafael , Peña-Miller Rafael , San Millán Alvaro 
Published: May 2021

AbstractPlasmid persistence in bacterial populations is strongly influenced by the fitness effects associated with plasmid carriage. However, plasmid fitness effects in wild-type bacterial hosts remain largely unexplored. In this study, we determined the fitness effects of the major antibiotic resistance plasmid pOXA-48_K8 in wild-type, ecologically compatible enterobacterial isolates from the human gut microbiota. Our results show that although pOXA-48_K8 produced an overall reduction in bacterial fitness, it produced small effects in most bacterial hosts, and even beneficial effects in several isolates. Moreover, genomic results showed a link between pOXA-48_K8 fitness effects and bacterial phylogeny, helping to explain plasmid epidemiology. Incorporating our fitness results into a simple population dynamics model revealed a new set of conditions for plasmid stability in bacterial communities, with plasmid persistence increasing with bacterial diversity and becoming less dependent on conjugation. These results help to explain the high prevalence of plasmids in the greatly diverse natural microbial communities.
Single nucleus multi-omics regulatory landscape of the murine pituitary
Authors: Ruf-Zamojski Frederique , Zhang Zidong , Zamojski Michel , Smith Gregory R. , Mendelev Natalia , Liu Hanqing , Nudelman German , Moriwaki Mika , Pincas Hanna , Castanon Rosa Gomez , Nair Venugopalan D. , Seenarine Nitish , Amper Mary Anne S. , Zhou Xiang , Ongaro Luisina , Toufaily Chirine , Schang Gauthier , Nery Joseph R. , Bartlett Anna , Aldridge Andrew , Jain Nimisha , Childs Gwen V. , Troyanskaya Olga G. , Ecker Joseph R. , Turgeon Judith L. , Welt Corrine K. , Bernard Daniel J. , Sealfon Stuart C. 
Published: May 2021

AbstractTo provide a multi-omics resource and investigate transcriptional regulatory mechanisms, we profile the transcriptome, chromatin accessibility, and methylation status of over 70,000 single nuclei (sn) from adult mouse pituitaries. Paired snRNAseq and snATACseq datasets from individual animals highlight a continuum between developmental epigenetically-encoded cell types and transcriptionally-determined transient cell states. Co-accessibility analysis-based identification of a putative Fshb cis-regulatory domain that overlaps the fertility-linked rs11031006 human polymorphism, followed by experimental validation illustrate the use of this resource for hypothesis generation. We also identify transcriptional and chromatin accessibility programs distinguishing each major cell type. Regulons, which are co-regulated gene sets sharing binding sites for a common transcription factor driver, recapitulate cell type clustering. We identify both cell type-specific and sex-specific regulons that are highly correlated with promoter accessibility, but not with methylation state, supporting the centrality of chromatin accessibility in shaping cell-defining transcriptional programs. The sn multi-omics atlas is accessible at snpituitaryatlas.princeton.edu.
Helium in diamonds unravels over a billion years of craton metasomatism
Authors: Weiss Yaakov , Kiro Yael , Class Cornelia , Winckler Gisela , Harris Jeff W. , Goldstein Steven L. 
Published: May 2021

AbstractChemical events involving deep carbon- and water-rich fluids impact the continental lithosphere over its history. Diamonds are a by-product of such episodic fluid infiltrations, and entrapment of these fluids as microinclusions in lithospheric diamonds provide unique opportunities to investigate their nature. However, until now, direct constraints on the timing of such events have not been available. Here we report three alteration events in the southwest Kaapvaal lithosphere using U-Th-He geochronology of fluid-bearing diamonds, and constrain the upper limit of He diffusivity (to D ≈ 1.8 × 10−19 cm2 s−1), thus providing a means to directly place both upper and lower age limits on these alteration episodes. The youngest, during the Cretaceous, involved highly saline fluids, indicating a relationship with late-Mesozoic kimberlite eruptions. Remnants of two preceding events, by a Paleozoic silicic fluid and a Proterozoic carbonatitic fluid, are also encapsulated in Kaapvaal diamonds and are likely coeval with major surface tectonic events (e.g. the Damara and Namaqua–Natal orogenies).
The double-stranded DNA-binding proteins TEBP-1 and TEBP-2 form a telomeric complex with POT-1
Authors: Dietz Sabrina , Almeida Miguel Vasconcelos , Nischwitz Emily , Schreier Jan , Viceconte Nikenza , Fradera-Sola Albert , Renz Christian , Ceron-Noriega Alejandro , Ulrich Helle D. , Kappei Dennis , Ketting René F. , Butter Falk 
Published: May 2021

AbstractTelomeres are bound by dedicated proteins, which protect them from DNA damage and regulate telomere length homeostasis. In the nematodeCaenorhabditis elegans, a comprehensive understanding of the proteins interacting with the telomere sequence is lacking. Here, we harnessed a quantitative proteomics approach to identify TEBP-1 and TEBP-2, two paralogs expressed in the germline and embryogenesis that associate to telomeres in vitro and in vivo.tebp-1andtebp-2mutants display strikingly distinct phenotypes:tebp-1mutants have longer telomeres than wild-type animals, whiletebp-2mutants display shorter telomeres and a Mortal Germline. Notably,tebp-1;tebp-2double mutant animals have synthetic sterility, with germlines showing signs of severe mitotic and meiotic arrest. Furthermore, we show that POT-1 forms a telomeric complex with TEBP-1 and TEBP-2, which bridges TEBP-1/-2 with POT-2/MRT-1. These results provide insights into the composition and organization of a telomeric protein complex inC. elegans.
Artificial intelligence-enabled fully automated detection of cardiac amyloidosis using electrocardiograms and echocardiograms
Authors: Goto Shinichi , Mahara Keitaro , Beussink-Nelson Lauren , Ikura Hidehiko , Katsumata Yoshinori , Endo Jin , Gaggin Hanna K. , Shah Sanjiv J. , Itabashi Yuji , MacRae Calum A. , Deo Rahul C. 
Published: May 2021

AbstractPatients with rare conditions such as cardiac amyloidosis (CA) are difficult to identify, given the similarity of disease manifestations to more prevalent disorders. The deployment of approved therapies for CA has been limited by delayed diagnosis of this disease. Artificial intelligence (AI) could enable detection of rare diseases. Here we present a pipeline for CA detection using AI models with electrocardiograms (ECG) or echocardiograms as inputs. These models, trained and validated on 3 and 5 academic medical centers (AMC) respectively, detect CA with C-statistics of 0.85–0.91 for ECG and 0.89–1.00 for echocardiography. Simulating deployment on 2 AMCs indicated a positive predictive value (PPV) for the ECG model of 3–4% at 52–71% recall. Pre-screening with ECG enhance the echocardiography model performance at 67% recall from PPV of 33% to PPV of 74–77%. In conclusion, we developed an automated strategy to augment CA detection, which should be generalizable to other rare cardiac diseases.
Inositol triphosphate-triggered calcium release blocks lipid exchange at endoplasmic reticulum-Golgi contact sites
Authors: Malek Mouhannad , Wawrzyniak Anna M. , Koch Peter , Lüchtenborg Christian , Hessenberger Manuel , Sachsenheimer Timo , Jang Wonyul , Brügger Britta , Haucke Volker 
Published: May 2021

AbstractVesicular traffic and membrane contact sites between organelles enable the exchange of proteins, lipids, and metabolites. Recruitment of tethers to contact sites between the endoplasmic reticulum (ER) and the plasma membrane is often triggered by calcium. Here we reveal a function for calcium in the repression of cholesterol export at membrane contact sites between the ER and the Golgi complex. We show that calcium efflux from ER stores induced by inositol-triphosphate [IP3] accumulation upon loss of the inositol 5-phosphatase INPP5A or receptor signaling triggers depletion of cholesterol and associated Gb3 from the cell surface, resulting in a blockade of clathrin-independent endocytosis (CIE) of Shiga toxin. This phenotype is caused by the calcium-induced dissociation of oxysterol binding protein (OSBP) from the Golgi complex and from VAP-containing membrane contact sites. Our findings reveal a crucial function for INPP5A-mediated IP3 hydrolysis in the control of lipid exchange at membrane contact sites.
1.5 °C degrowth scenarios suggest the need for new mitigation pathways
Authors: Keyßer Lorenz T. , Lenzen Manfred 
Published: May 2021

Abstract1.5  °C scenarios reported by the Intergovernmental Panel on Climate Change (IPCC) rely on combinations of controversial negative emissions and unprecedented technological change, while assuming continued growth in gross domestic product (GDP). Thus far, the integrated assessment modelling community and the IPCC have neglected to consider degrowth scenarios, where economic output declines due to stringent climate mitigation. Hence, their potential to avoid reliance on negative emissions and speculative rates of technological change remains unexplored. As a first step to address this gap, this paper compares 1.5  °C degrowth scenarios with IPCC archetype scenarios, using a simplified quantitative representation of the fuel-energy-emissions nexus. Here we find that the degrowth scenarios minimize many key risks for feasibility and sustainability compared to technology-driven pathways, such as the reliance on high energy-GDP decoupling, large-scale carbon dioxide removal and large-scale and high-speed renewable energy transformation. However, substantial challenges remain regarding political feasibility. Nevertheless, degrowth pathways should be thoroughly considered.
Elp2 mutations perturb the epitranscriptome and lead to a complex neurodevelopmental phenotype
Authors: Kojic Marija , Gawda Tomasz , Gaik Monika , Begg Alexander , Salerno-Kochan Anna , Kurniawan Nyoman D. , Jones Alun , Drożdżyk Katarzyna , Kościelniak Anna , Chramiec-Głąbik Andrzej , Hediyeh-Zadeh Soroor , Kasherman Maria , Shim Woo Jun , Sinniah Enakshi , Genovesi Laura A. , Abrahamsen Rannvá K. , Fenger Christina D. , Madsen Camilla G. , Cohen Julie S. , Fatemi Ali , Stark Zornitza , Lunke Sebastian , Lee Joy , Hansen Jonas K. , Boxill Martin F. , Keren Boris , Marey Isabelle , Saenz Margarita S. , Brown Kathleen , Alexander Suzanne A. , Mureev Sergey , Batzilla Alina , Davis Melissa J. , Piper Michael , Bodén Mikael , Burne Thomas H. J. , Palpant Nathan J. , Møller Rikke S. , Glatt Sebastian , Wainwright Brandon J. 
Published: May 2021

AbstractIntellectual disability (ID) and autism spectrum disorder (ASD) are the most common neurodevelopmental disorders and are characterized by substantial impairment in intellectual and adaptive functioning, with their genetic and molecular basis remaining largely unknown. Here, we identify biallelic variants in the gene encoding one of the Elongator complex subunits, ELP2, in patients with ID and ASD. Modelling the variants in mice recapitulates the patient features, with brain imaging and tractography analysis revealing microcephaly, loss of white matter tract integrity and an aberrant functional connectome. We show that the Elp2 mutations negatively impact the activity of the complex and its function in translation via tRNA modification. Further, we elucidate that the mutations perturb protein homeostasis leading to impaired neurogenesis, myelin loss and neurodegeneration. Collectively, our data demonstrate an unexpected role for tRNA modification in the pathogenesis of monogenic ID and ASD and define Elp2 as a key regulator of brain development.
Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features
Authors: Dejima Hitoshi , Hu Xin , Chen Runzhe , Zhang Jiexin , Fujimoto Junya , Parra Edwin R. , Haymaker Cara , Hubert Shawna M. , Duose Dzifa , Solis Luisa M. , Su Dan , Fukuoka Junya , Tabata Kazuhiro , Pham Hoa H. N. , Mcgranahan Nicholas , Zhang Baili , Ye Jie , Ying Lisha , Little Latasha , Gumbs Curtis , Chow Chi-Wan , Estecio Marcos Roberto , Godoy Myrna C. B. , Antonoff Mara B. , Sepesi Boris , Pass Harvey I. , Behrens Carmen , Zhang Jianhua , Vaporciyan Ara A. , Heymach John V. , Scheet Paul , Lee J. Jack , Wu Jia , Futreal P. Andrew , Reuben Alexandre , Kadara Humam , Wistuba Ignacio I. , Zhang Jianjun 
Published: May 2021

AbstractThe mechanism by which anti-cancer immunity shapes early carcinogenesis of lung adenocarcinoma (ADC) is unknown. In this study, we characterize the immune contexture of invasive lung ADC and its precursors by transcriptomic immune profiling, T cell receptor (TCR) sequencing and multiplex immunofluorescence (mIF). Our results demonstrate that anti-tumor immunity evolved as a continuum from lung preneoplasia, to preinvasive ADC, minimally-invasive ADC and frankly invasive lung ADC with a gradually less effective and more intensively regulated immune response including down-regulation of immune-activation pathways, up-regulation of immunosuppressive pathways, lower infiltration of cytotoxic T cells (CTLs) and anti-tumor helper T cells (Th), higher infiltration of regulatory T cells (Tregs), decreased T cell clonality, and lower frequencies of top T cell clones in later-stages. Driver mutations, chromosomal copy number aberrations (CNAs) and aberrant DNA methylation may collectively impinge host immune responses and facilitate immune evasion, promoting the outgrowth of fit subclones in preneoplasia into dominant clones in invasive ADC.
Micron-scale phenomena observed in a turbulent laser-produced plasma
Authors: Rigon G. , Albertazzi B. , Pikuz T. , Mabey P. , Bouffetier V. , Ozaki N. , Vinci T. , Barbato F. , Falize E. , Inubushi Y. , Kamimura N. , Katagiri K. , Makarov S. , Manuel M. J.-E. , Miyanishi K. , Pikuz S. , Poujade O. , Sueda K. , Togashi T. , Umeda Y. , Yabashi M. , Yabuuchi T. , Gregori G. , Kodama R. , Casner A. , Koenig M. 
Published: May 2021

AbstractTurbulence is ubiquitous in the universe and in fluid dynamics. It influences a wide range of high energy density systems, from inertial confinement fusion to astrophysical-object evolution. Understanding this phenomenon is crucial, however, due to limitations in experimental and numerical methods in plasma systems, a complete description of the turbulent spectrum is still lacking. Here, we present the measurement of a turbulent spectrum down to micron scale in a laser-plasma experiment. We use an experimental platform, which couples a high power optical laser, an x-ray free-electron laser and a lithium fluoride crystal, to study the dynamics of a plasma flow with micrometric resolution (~1μm) over a large field of view (>1 mm2). After the evolution of a Rayleigh–Taylor unstable system, we obtain spectra, which are overall consistent with existing turbulent theory, but present unexpected features. This work paves the way towards a better understanding of numerous systems, as it allows the direct comparison of experimental results, theory and numerical simulations.
Portable bioluminescent platform for in vivo monitoring of biological processes in non-transgenic animals
Authors: Yevtodiyenko Aleksey , Bazhin Arkadiy , Khodakivskyi Pavlo , Godinat Aurelien , Budin Ghyslain , Maric Tamara , Pietramaggiori Giorgio , Scherer Sandra S. , Kunchulia Marina , Eppeldauer George , Polyakov Sergey V. , Francis Kevin P. , Bryan Jeffrey N. , Goun Elena A. 
Published: May 2021

AbstractBioluminescent imaging (BLI) is one of the most powerful and widely used preclinical imaging modalities. However, the current technology relies on the use of transgenic luciferase-expressing cells and animals and therefore can only be applied to a limited number of existing animal models of human disease. Here, we report the development of a “portable bioluminescent” (PBL) technology that overcomes most of the major limitations of traditional BLI. We demonstrate that the PBL method is capable of noninvasive measuring the activity of both extracellular (e.g., dipeptidyl peptidase 4) and intracellular (e.g., cytochrome P450) enzymes in vivo in non-luciferase-expressing mice. Moreover, we successfully utilize PBL technology in dogs and human cadaver, paving the way for the translation of functional BLI to the noninvasive quantification of biological processes in large animals. The PBL methodology can be easily adapted for the noninvasive monitoring of a plethora of diseases across multiple species.