bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple quantitative trait loci contribute tolerance to bacterial canker incited byPseudomonas syringaepv.actinidiaein kiwifruit (Actinidia chinensis)
Authors: Tahir Jibran , Hoyte Stephen , Bassett Heather , Brendolise Cyril , Chatterjee Abhishek , Templeton Kerry , Deng Cecilia , Crowhurst Ross , Montefiori Mirco , Morgan Ed , Wotton Andrew , Funnell Keith , Wiedow Claudia , Knaebel Mareike , Hedderley Duncan , Vanneste Joel , McCallum John , Hoeata Kirsten , Chagné David , Gea Luis , Gardiner Susan E. 
Published: January 2019

AbstractPseudomonas syringaepv.actinidiae(Psa) Biovar 3, a virulent, canker-inducing pathogen is an economic threat to the kiwifruit (Actinidiaspp.) industry worldwide. The commercially grown diploid (2x)A. chinensisvar.chinensisis more susceptible to Psa than tetraploid and hexaploid kiwifruit. However information on the genetic loci modulatingPsaresistance in kiwifruit is not available. Here we report mapping of quantitative trait loci (QTLs) regulating tolerance to Psa in a diploid kiwifruit population, derived from a cross between an elite Psa-susceptible ‘Hort16A’ and a tolerant male breeding parent P1. Using high-density genetic maps and intensive phenotyping, we identified a single QTL for Psa tolerance on Linkage Group (LG) 27 of ‘Hort16A’ revealing 16-19% phenotypic variance and candidate alleles for susceptibility and tolerance at this loci. In addition, six minor QTLs were identified in P1 on distinct LGs, exerting 4-9% variance. Complete tolerance in the F1 population is attained by additive effects from ‘Hort16A’ and P1 QTLs providing evidence that divergent genetic pathways fend-off virulent Psa strain. Two different bioassays further identified new QTLs for tissue-specific responses to Psa. Transcriptome analysis of Psa-tolerant and susceptible genotypes in field revealed hallmarks of basal defense and provided candidate RNA-biomarkers for screening Psa tolerance.
Hybrid optical gating for long-term 3D time-lapse imaging of the beating embryonic zebrafish heart
Authors: Taylor Jonathan M. , Nelson Carl J. , Bruton Finnius A. , Baghbadrani Aryan K. , Buckley Charlotte , Tucker Carl S. , Mullins John J. , Denvir Martin A. 
Published: January 2019

AbstractThree-dimensional fluorescence time-lapse imaging of structural, cellular and sub-cellular processes in the beating heart is an increasingly achievable goal using the latest imaging and computational techniques. However, previous approaches have had significant limitations. Temporarily arresting the heart using drugs disrupts the heart’s physiological state, and the use of ultra-high frame-rates for fluorescence image acquisition causes phototoxic cell damage. Real-time triggered imaging, synchronized to a specific phase in the cardiac-cycle, can computationally “freeze” the heart to acquire the minimal number of fluorescence images required for 3D time-lapse imaging. However, until now no solution has been able to maintain phase-lock to the same point in the cardiac cycle for more than about one hour. Our new hybrid optical gating system maintains phase-lock for up to 24 h, acquiring synchronized 3D+time video stacks of the unperturbed heartin vivo. This approach has enabled us to observe detailed developmental, structural, cellular and subcellular processes, including live cell division and cell fate tracking, in the embryonic zebrafish heart using transgenic fish lines expressing cell-specific fluorophores. We show that our approach not only provides high spatial and temporal resolution 3D-imaging, but also avoids phototoxic injury, where alternative approaches induce measurable harm. This provides superb cellular and subcellular imaging of the heart while it is beating in its normal physiological state, and opens up new and exciting opportunities for further study in the heart and other moving cellular and subcellular structuresin vivo.
CHAP: A versatile tool for the structural and functional annotation of ion channel pores
Authors: Klesse Gianni , Rao Shanlin , Sansom Mark S.P. , Tucker Stephen J. 
Published: January 2019

AbstractThe regulation of ion channel and transporter function requires the modulation of energetic barriers or ‘gates’ within their transmembrane pathways. However, despite the ever-increasing number of available structures, our understanding of these barriers is often simply determined from calculating the physical dimensions of the pore. Such approaches (e.g. the HOLE program) have worked very well in the past, but there is now considerable evidence that the unusual behaviour of water within the narrow hydrophobic spaces found within many ion channel pores can also produce energetic barriers to ion conduction without requiring physical occlusion of the permeation pathway. Several different classes of ion channels have now been shown to exploit this principle of ‘hydrophobic gating’ to regulate ion flow. However, measurement of pore radius alone is unable to identify such barriers and new tools are required for more accurate functional annotation of an exponentially increasing number of ion channel structures. We have previously shown how molecular dynamics simulations of water behaviour can be used as a proxy to accurately predict hydrophobic gates. Here we now present a new and highly versatile computational tool, the Channel Annotation Package (CHAP) that implements this methodology to predict the conductive status of new ion channel structures.
A cellular census of healthy lung and asthmatic airway wall identifies novel cell states in health and disease
Authors: Vieira Braga F.A. , Kar G. , Berg M. , Carpaij O.A. , Polanski K. , Simon L.M. , Brouwer S. , Gomes T. , Hesse L. , Jiang J. , Fasouli E.S. , Efremova M. , Vento-Tormo R. , Affleck K. , Palit S. , Strzelecka P. , Firth H.V. , Mahbubani K.T.A. , Cvejic A. , Meyer K.B. , Saeb-Parsy K. , Luinge M. , Brandsma C.-A. , Timens W. , Angelidis I. , Strunz M. , Koppelman G.H. , van Oosterhout A.J. , Schiller H.B. , Theis F.J. , van den Berge M. , Nawijn M.C. , Teichmann S.A. 
Published: January 2019

SummaryHuman lungs enable efficient gas exchange, and form an interface with the environment which depends on mucosal immunity for protection against infectious agents. Tightly controlled interactions between structural and immune cells are required to maintain lung homeostasis. Here, we use single cell transcriptomics to chart the cellular landscape of upper and lower airways and lung parenchyma in health. We report location-dependent airway epithelial cell states, and a novel subset of tissue-resident memory T cells. In lower airways of asthma patients, mucous cell hyperplasia is shown to stem from a novel mucous ciliated cell state, as well as goblet cell hyperplasia. We report presence of pathogenic effector Th2 cells in asthma, and find evidence for type-2 cytokines in maintaining the altered epithelial cell states. Unbiased analysis of cell-cell interactions identify a shift from airway structural cell communication in health to a Th2-dominated interactome in asthma.
Wikipedia network analysis of cancer interactions and world influence
Authors: Rollin Guillaume , Lages José , Shepelyansky Dima L. 
Published: January 2019

AbstractWe apply the Google matrix algorithms for analysis of interactions and influence of 37 cancer types, 203 cancer drugs and 195 world countries using the network of 5 416 537 English Wikipedia articles with all their directed hyperlinks. The PageRank algorithm provides the importance order of cancers which has 60% and 70% overlaps with the top 10 cancers extracted from World Health Organization GLOBOCAN 2018 and Global Burden of Diseases Study 2017, respectively. The recently developed reduced Google matrix algorithm gives networks of interactions between cancers, drugs and countries taking into account all direct and indirect links between these selected 435 entities. These reduced networks allow to obtain sensitivity of countries to specific cancers and drugs. The strongest links between cancers and drugs are in good agreement with the approved medical prescriptions of specific drugs to specific cancers. We argue that this analysis of knowledge accumulated in Wikipedia provides useful complementary global information about interdependencies between cancers, drugs and world countries.
MPRAnalyze - A statistical framework for Massively Parallel Reporter Assays
Authors: Ashuach Tal , Fischer David Sebastian , Kreimer Anat , Ahituv Nadav , Theis Fabian , Yosef Nir 
Published: January 2019

AbstractMassively parallel reporter assays (MPRAs) are a technique that enables testing thousands of regulatory DNA sequences and their variants in a single, quantitative experiment. Despite growing popularity, there is lack of statistical methods that account for the different sources of uncertainty inherent to these assays, thus effectively leveraging their promise. Development of such methods could help enhance our ability to identify regulatory sequences in the genome, understand their function under various setting, and ultimately gain a better understanding of how the regulatory code and its alteration lead to phenotypic consequence.Here we present MPRAnalyze: a statistical framework dedicated to analyzing MPRA count data. MPRAnalyze addresses the major questions that are posed in the context of MPRA experiments: estimating the magnitude of the effect of a regulatory sequence in a single condition setting, and comparing differential activity of regulatory sequences across multiple conditions. The framework uses a nested construction of generalized linear models to account for uncertainty in both DNA and RNA observations, controls for various sources of unwanted variation, and incorporates negative controls for robust hypothesis testing, thereby providing clear quantitative answers in complex experimental settings.We demonstrate the robustness, accuracy and applicability of MPR-Analyze on simulated data and published data sets and compare it against the existing analysis methodologies. MPRAnalyze is implemented as an R package and is publicly available through Bioconductor [1].
A metabolic dependency for host isoprenoids in the obligate intracellular pathogenRickettsia parkeriunderlies a sensitivity for the statin class of host-targeted therapeutics
Authors: Ahyong Vida , Berdan Charles A. , Nomura Daniel K. , Welch Matthew D. 
Published: January 2019

AbstractGram-negative bacteria in the order Rickettsiales are obligate intracellular parasites that cause human diseases such typhus and spotted fever. They have evolved a dependence on essential nutrients and metabolites from the host cell as a consequence of extensive genome streamlining. However, it remains largely unknown which nutrients they require and whether their metabolic dependency can be exploited therapeutically. Here, we describe a genetic rewiring of bacterial isoprenoid biosynthetic pathways in the Rickettsiales that has resulted from reductive genome evolution. We further investigated whether the spotted fever groupRickettsiaspeciesRickettsia parkeriscavenges isoprenoid precursors directly from the host. Using targeted mass spectrometry in uninfected and infected cells, we found decreases in host isoprenoid products and concomitant increases in bacterial isoprenoid metabolites. Additionally, we report that bacterial growth is prohibited by inhibition of the host isoprenoid pathway with the statins class of drugs. We show that growth inhibition correlates with changes in bacterial size and shape that mimic those caused by antibiotics that inhibit peptidoglycan biosynthesis, suggesting statins inhibit cell wall synthesis. Altogether, our results describe an Achilles’ heel of obligate intracellular pathogens that can be exploited with host-targeted therapeutics that interfere with metabolic pathways required for bacterial growth.ImportanceObligate intracellular parasites, which include viruses as well as certain bacteria and eukaryotes, extract essential nutrients and metabolites from their host cell. As a result, these pathogens have often lost essential biosynthetic pathways and are metabolically dependent on the host. In this study, we describe a metabolic dependency of the bacterial pathogenRickettsia parkerion host isoprenoid molecules that are used in the biosynthesis of downstream products including cholesterol, steroid hormones, and heme. Bacteria make products from isoprenoids such as an essential lipid carrier for making the bacterial cell wall. We show that bacterial metabolic dependency can represent an Achilles’ heel, and that inhibiting host isoprenoid biosynthesis with the FDA-approved statin class of drugs inhibits bacterial growth by interfering with the integrity of the cell wall. This work highlights a potential to treat infections by obligate intracellular pathogens through inhibition of host biosynthetic pathways that are susceptible to parasitism.
Reactive Dicarbonyl Scavenging Effectively Reduces MPO-Mediated Oxidation of HDL and Preserves HDL Atheroprotective Functions
Authors: Huang Jiansheng , Yancey Patricia G. , Tao Huan , Borja Mark , Smith Loren , Kon Valentina , Davies Sean S. , Linton MacRae F. 
Published: January 2019

AbstractHigh-density lipoprotein (HDL) is atheroprotective by mediating cholesterol efflux, anti-inflammatory, and anti-oxidation functions. Atheroprotective functions of HDL are related to the activity of HDL-associated enzymes such as paraoxonase 1 (PON1). We examined the impact of inhibition of myeloperoxidase (MPO)-mediated HDL oxidation by PON1 on HDL malondialdehyde (MDA) content and HDL function. In the presence of PON1, crosslinking of apoAI in response to MPO-mediated oxidation of HDL was abolished and MDA-HDL adduct levels were decreased. In addition, PON1 prevented the impaired cholesterol efflux capacity of MPO-oxidized HDL fromApoe-/-macrophages. Direct modification of HDL with MDA increased apoAI crosslinking and reduced the cholesterol efflux capacity in a dose dependent manner. In addition, MDA modification of HDL reduced its anti-inflammatory function compared to native HDL as the expression of IL-1β and IL6 increased by 3-(p<0.05) and 1.8-fold (p<0.05) inApoe-/-macrophages in response to LPS. MDA-HDL also had impaired ability to increase PON1 activity. Importantly, HDL from subjects with familial hypercholesterolemia (FH-HDL) versus controls had increased MDA-apoAI adducts, and normalization of the PON1 activity to PON1 mass revealed a 24 % (p<0.05) decrease in specific activity indicating that PON1 activity is also impaired in FH. Consistent with the impaired PON1 activity and increased MDA-apoAI, FH-HDL induced a pro-inflammatory response inApoe-/-macrophages compared to incubation with LPS alone. FH-HDL versus control HDL also had an impaired ability to promote cholesterol efflux fromApoe-/-macrophages. Interestingly, reactive dicarbonyl scavengers effectively abolished MPO-mediated apoAI crosslinking, MDA adduct formation, and improved cholesterol efflux capacity. Importantly, in vivo treatment of hypercholesterolemic mice with reactive dicarbonyl scavengers effectively reduced MDA-HDL adduct formation and increased PON1 activity and HDL cholesterol efflux capacity, supporting a therapeutic potential of reactive carbonyl scavenging in maintaining HDL function.
Comparative identification of microRNAs inApis cerana ceranaworkers’ midguts responding toNosema ceranaeinvasion
Authors: Chen Dafu , Du Yu , Chen Huazhi , Wang Haipeng , Xiong Cuiling , Zheng Yanzhen , Hou Chunsheng , Diao Qingyun , Guo Rui 
Published: January 2019

AbstractMicroRNAs (miRNAs) are endogenous small noncoding RNAs that post transcriptionally regulate gene expression and are involved in many biological processes including host-pathogen interactions. However, the potential role of miRNAs in the responses of eastern honeybees toNosema ceranaeinvasion is completely unknown. Here, the expression profiles and differentially expressed miRNAs (DEmiRNAs) in the midguts ofApis cerana ceranaworkers 7 and 10 days post infection (dpi) withN. ceranaewere investigated via small RNA sequencing and bioinformatics. In total, 529 miRNAs highly conserved between various species and 25 novel miRNAs with varied expressions were identified for the first time. In addition, stem-loop RT-PCR confirmed the expression of 16 predicted miRNAs, validating their existence. Eight up-regulated miRNAs and six down-regulated miRNAs were detected in midguts at 7 dpi, while nine and three miRNAs were significantly up-regulated and down-regulated, respectively, in midguts at 10 dpi. In addition, Venn analysis showed that five DEmiRNAs were shared, while nine and seven DEmiRNAs were specifically expressed in midguts at 7 and 10 dpi, respectively. Gene ontology analysis suggested that a portion of the DEmiRNAs and corresponding target genes were involved in various biological processes, cellular components, and molecular functions including immune system processes and response to stimulus and signaling. Moreover, KEGG pathway analysis shed light on the potential functions of some DEmiRNAs in the regulation of target genes engaged in material and energy metabolism, cellular immunity such as endocytosis and phagosome, and the humoral immune system, including the Jak-STAT and MAPK signaling pathways. Further investigation demonstrated a complex regulation network between DEmiRNAs and their target mRNAs, with miR-598-y, miR-252-y, miR-92-x and miR-3654-y at the center of the network, implying their key parts in host responses. This comprehensive miRNA transcriptome analysis demonstrated thatN. ceranaeinvasion influenced the expression of miRNAs in the midguts ofA. c. ceranaeworkers; the results can not only facilitate future exploration of the regulatory roles and mechanisms of miRNAs in hosts’ responses, especially their immune responses toN. ceranae, but also provide potential candidates for further investigation of the molecular mechanisms underlying eastern honeybee-microsporidian interactions.
Revealing the ocean metabolome with mass spectrometry
Authors: Sogin E. Maggie , Puskas Erik , Dubilier Nicole , Liebeke Manuel 
Published: January 2019

AbstractAll life exchanges molecules with its environment. While these metabolites are commonly measured in terrestrial and limnic ecosystems, the presence of salt in marine habitats has hampered quantitative analyses of the ocean metabolome. To overcome these limitations, we developed SeaMet, a gas chromatography-mass spectrometry (GC-MS) method that detects hundreds of metabolites down to nano-molar concentrations in less than one milliliter of seawater. Using a set of metabolites dissolved in artificial seawater to benchmark our method, we show metabolite signal detection increased on average across ions by 324 fold in comparison to standard GC-MS methods. Our observed signal improvement occurred across tested metabolite classes and provides reproducible and quantifiable results. To showcase the capabilities of our method, we used SeaMet to explore the production and consumption of metabolites during culture of a heterotrophic bacteria that is widespread in the North Sea. Our approach revealed successional uptake of amino acids, while sugars were not consumed, and highlight the power of metabolomics in providing insights into nutrient uptake and energy conservation in marine microorganisms. We also applied SeaMet to explore the in situ metabolome of coral reef and mangrove sediment porewaters. Despite the fact that these ecosystems occur in nutrient-poor waters, we uncovered a remarkable diversity and abundance of sugars and fatty acids, compounds predicted to be rapidly consumed by marine microorganisms. Our method advances marine metabolomics by enabling the unbiased, and quantitative analysis of marine metabolites, and will help provide new insights into carbon cycle dynamics and ocean biogeochemistry.SignificanceMetabolites are the chemical currency of cellular metabolism across all domains of life. However, describing metabolites that occur in the oceans is lagging behind similar studies conducted on land. The central challenge in marine metabolomics is that salt prevents the comprehensive analysis of metabolites in seawater. We developed a method, SeaMet, that overcomes the limitations of salt on metabolite detection. SeaMet provides a time and cost efficient method, using gas chromatography-mass spectrometry, for the reproducible identification and quantification of a broad range of marine compounds. Considering the oceans contain the largest organic carbon pool on Earth, describing the marine metabolome is critical for understanding the drivers behind element cycles, biotic interactions, ecosystem function, and atmospheric CO2storage.
Estimating seed dispersal distance: a comparison of methods using animal movement and plant genetic data on two primate-dispersed Neotropical plant species
Authors: Gelmi-Candusso Tiziana A. , Bialozyt Ronald , Slana Darja , Gómez Ricardo Zárate , Heymann Eckhard W. , Heer Katrin 
Published: January 2019

AbstractSeed dispersal distances (SDD) critically influence the survival of seedlings, spatial patterns of genetic diversity within plant populations and gene flow among plant populations. In tropical forests, a large percentage of seeds is dispersed by animals, and their foraging behaviour and movement patterns determine SDD. Direct observations of seed dispersal events by animals in natural plant populations are mostly constrained by the high mobility and low visibility of their vectors. Therefore, diverse alternative methods are used to estimate SDD, but direct comparisons of these approaches within the same seed dispersal system are mostly missing.In this study, we take advantage of two plant species with different life history traits, Leonia cymosa and Parkia panurensis that are exclusively dispersed by two tamarin species, Saguinus mystax and Leontocebus nigrifrons (Callitrichidae) at our study site in the Peruvian Amazon. We compare SDD estimates obtained from direct observations, genetic identification of mother plants from seed coats, parentage analysis of seedlings, and modelling approaches, including the combination of movement data and gut passage times and individual-based modelling.We detect differences between SDD estimates that can be linked to the processes relevant at different phases of the seed dispersal loop covered by the respective approaches. Despite these differences, SDD estimates for P. panurensis are consistently lower than for L. cymosa which is likely related to differences in fruit characteristics and fruit abundance, factors that influence gut passage time, foraging behaviour and movement patterns of the tamarins.Our comparisons allow setting SDD estimates from studies using different methodological approaches into the seed dispersal loop context, thus improving comparability of methodologically different studies and method applicability.