bluuebunny/crossref_metadata_2025_split huggingface dataset:
Learning a Health Knowledge Graph from Electronic Medical Records
Authors: Rotmensch Maya , Halpern Yoni , Tlimat Abdulhakim , Horng Steven , Sontag David 
Published: July 2017

AbstractDemand for clinical decision support systems in medicine and self-diagnostic symptom checkers has substantially increased in recent years. Existing platforms rely on knowledge bases manually compiled through a labor-intensive process or automatically derived using simple pairwise statistics. This study explored an automated process to learn high quality knowledge bases linking diseases and symptoms directly from electronic medical records. Medical concepts were extracted from 273,174 de-identified patient records and maximum likelihood estimation of three probabilistic models was used to automatically construct knowledge graphs: logistic regression, naive Bayes classifier and a Bayesian network using noisy OR gates. A graph of disease-symptom relationships was elicited from the learned parameters and the constructed knowledge graphs were evaluated and validated, with permission, against Google’s manually-constructed knowledge graph and against expert physician opinions. Our study shows that direct and automated construction of high quality health knowledge graphs from medical records using rudimentary concept extraction is feasible. The noisy OR model produces a high quality knowledge graph reaching precision of 0.85 for a recall of 0.6 in the clinical evaluation. Noisy OR significantly outperforms all tested models across evaluation frameworks (p < 0.01).
Effects of cardiac timing and peripheral resistance on measurement of pulse wave velocity for assessment of arterial stiffness
Authors: Xiao Hanguang , Butlin Mark , Tan Isabella , Avolio Alberto 
Published: July 2017

AbstractTo investigate the effects of heart rate (HR), left ventricular ejection time (LVET) and wave reflection on arterial stiffness as assessed by pulse wave velocity (PWV), a pulse wave propagation simulation system (PWPSim) based on the transmission line model of the arterial tree was developed and was applied to investigate pulse wave propagation. HR, LVET, arterial elastic modulus and peripheral resistance were increased from 60 to 100 beats per minute (bpm), 0.1 to 0.45 seconds, 0.5 to 1.5 times and 0.5 to 1.5 times of the normal value, respectively. Carotid-femoral PWV (cfPWV) and brachial-ankle PWV (baPWV) were calculated by intersecting tangent method (cfPWVtan and baPWVtan), maximum slope (cfPWVmax and baPWVmax), and using the Moens-Korteweg equation ($${\bf{cfPW}}{{\bf{V}}}_{{{\bf{c}}}_{{\bf{0}}}}$$
cfPW

V

c

0

and $${\bf{baPW}}{{\bf{V}}}_{{{\bf{c}}}_{{\bf{0}}}}$$
baPW

V

c

0

). Results showed cfPWV and baPWV increased significantly with arterial elastic modulus but did not increase with HR when using a constant elastic modulus. However there were significant LVET dependencies of cfPWVtan and baPWVtan (0.17 ± 0.13 and 0.17 ± 0.08 m/s per 50 ms), and low peripheral resistance dependencies of cfPWVtan, cfPWVmax, baPWVtan and baPWVmax (0.04 ± 0.01, 0.06 ± 0.04, 0.06 ± 0.03 and 0.09 ± 0.07 m/s per 10% peripheral resistance), respectively. This study demonstrated that LVET dominates the effect on calculated PWV compared to HR and peripheral resistance when arterial elastic modulus is constant.
Remarkable hexafunctional anion receptor with operational urea-based inner cleft and thiourea-based outer cleft: Novel design with high-efficiency for sulfate binding
Authors: Emami Khansari Maryam , Mirchi Ali , Pramanik Avijit , Johnson Corey R. , Leszczynski Jerzy , Hossain Md. Alamgir 
Published: July 2017

AbstractThe recognition of anions by designed receptors has attracted much attention in recent days. In particular, the selective binding of sulfate with artificial receptors is important because of its relevance to many biological and environmental applications. However, the development of organized molecular receptors with high-efficiency for sulfate binding still remains a significant challenge. We report a novel para-phenylene-bridged hexafunctional tripodal receptor that contains a urea-based inner cleft and a thiourea-based outer cleft, providing perfect sites for step-wise binding of two anions within a single cavity. The new receptor was synthesized in a three-step process, and was investigated for its anion binding properties by 1H NMR titrations, 2D NOESY experiments and computational studies. As indicated by solution binding studies, the receptor selectively binds sulfate over other oxoanions, forming a 1:2 stoichiometric complex that is stabilized via strong H-bonding interactions. High-level DFT calculations reveal that the receptor, owing to the enhanced H-bonding ability of thiourea groups, initially encapsulates one sulfate in its thiourea-based outer cleft, followed by a second encapsulation in its urea-based inner cleft. Such a functionalized receptor with the unique combination of urea-based cleft and thiourea-based cleft in a single receptor has not been reported previously.
Deletion of the celA gene in Aspergillus nidulans triggers overexpression of secondary metabolite biosynthetic genes
Authors: Guerriero Gea , Silvestrini Lucia , Legay Sylvain , Maixner Frank , Sulyok Michael , Hausman Jean-Francois , Strauss Joseph 
Published: July 2017

AbstractAlthough much progress has been made in the study of cell wall biosynthetic genes in the model filamentous fungus Aspergillus nidulans, there are still targets awaiting characterization. An example is the gene celA (ANIA_08444) encoding a putative mixed linkage glucan synthase. To characterize the role of celA, we deleted it in A. nidulans, analyzed the phenotype of the mycelium and performed RNA-Seq. The strain shows a very strong phenotype, namely “balloons” along the hyphae and aberrant conidiophores, as well as an altered susceptibility to cell wall drugs. These data suggest a potential role of the gene in cell wall-related processes. The Gene Ontology term Enrichment analysis shows increased expression of secondary metabolite biosynthetic genes (sterigmatocystin in particular) in the deleted strain. Our results show that the deletion of celA triggers a strong phenotype reminiscent of cell wall-related aberrations and the upregulation of some secondary metabolite gene clusters in A. nidulans.
Sphingomimetic multiple sclerosis drug FTY720 activates vesicular synaptobrevin and augments neuroendocrine secretion
Authors: Darios Frederic D. , Jorgacevski Jernej , Flašker Ajda , Zorec Robert , García-Martinez Virginia , Villanueva José , Gutiérrez Luis M. , Leese Charlotte , Bal Manjot , Nosyreva Elena , Kavalali Ege T. , Davletov Bazbek 
Published: July 2017

AbstractNeurotransmission and secretion of hormones involve a sequence of protein/lipid interactions with lipid turnover impacting on vesicle trafficking and ultimately fusion of secretory vesicles with the plasma membrane. We previously demonstrated that sphingosine, a sphingolipid metabolite, promotes formation of the SNARE complex required for membrane fusion and also increases the rate of exocytosis in isolated nerve terminals, neuromuscular junctions, neuroendocrine cells and in hippocampal neurons. Recently a fungi-derived sphingosine homologue, FTY720, has been approved for treatment of multiple sclerosis. In its non-phosphorylated form FTY720 accumulates in the central nervous system, reaching high levels which could affect neuronal function. Considering close structural similarity of sphingosine and FTY720 we investigated whether FTY720 has an effect on regulated exocytosis. Our data demonstrate that FTY720 can activate vesicular synaptobrevin for SNARE complex formation and enhance exocytosis in neuroendocrine cells and neurons.
A new approach for ratiometric in vivo calcium imaging of microglia
Authors: Brawek Bianca , Liang Yajie , Savitska Daria , Li Kaizhen , Fomin-Thunemann Natalie , Kovalchuk Yury , Zirdum Elizabeta , Jakobsson Johan , Garaschuk Olga 
Published: July 2017

AbstractMicroglia, resident immune cells of the brain, react to the presence of pathogens/danger signals with a large repertoire of functional responses including morphological changes, proliferation, chemotaxis, production/release of cytokines, and phagocytosis. In vitro studies suggest that many of these effector functions are Ca2+-dependent, but our knowledge about in vivo Ca2+ signalling in microglia is rudimentary. This is mostly due to technical reasons, as microglia largely resisted all attempts of in vivo labelling with Ca2+ indicators. Here, we introduce a novel approach, utilizing a microglia-specific microRNA-9-regulated viral vector, enabling the expression of a genetically-encoded ratiometric Ca2+ sensor Twitch-2B in microglia. The Twitch-2B-assisted in vivo imaging enables recording of spontaneous and evoked microglial Ca2+ signals and allows for the first time to monitor the steady state intracellular Ca2+ levels in microglia. Intact in vivo microglia show very homogenous and low steady state intracellular Ca2+ levels. However, the levels increase significantly after acute slice preparation and cell culturing along with an increase in the expression of activation markers CD68 and IL-1β. These data identify the steady state intracellular Ca2+ level as a versatile microglial activation marker, which is highly sensitive to the cell’s environment.
An ecological and digital epidemiology analysis on the role of human behavior on the 2014 Chikungunya outbreak in Martinique
Authors: Roche Benjamin , Gaillard Béatrice , Léger Lucas , Pélagie-Moutenda Renélise , Sochacki Thomas , Cazelles Bernard , Ledrans Martine , Blateau Alain , Fontenille Didier , Etienne Manuel , Simard Frédéric , Salathé Marcel , Yébakima André 
Published: July 2017

AbstractUnderstanding the spatio-temporal dynamics of endemic infections is of critical importance for a deeper understanding of pathogen transmission, and for the design of more efficient public health strategies. However, very few studies in this domain have focused on emerging infections, generating a gap of knowledge that hampers epidemiological response planning. Here, we analyze the case of a Chikungunya outbreak that occurred in Martinique in 2014. Using time series estimates from a network of sentinel practitioners covering the entire island, we first analyze the spatio-temporal dynamics and show that the largest city has served as the epicenter of this epidemic. We further show that the epidemic spread from there through two different propagation waves moving northwards and southwards, probably by individuals moving along the road network. We then develop a mathematical model to explore the drivers of the temporal dynamics of this mosquito-borne virus. Finally, we show that human behavior, inferred by a textual analysis of messages published on the social network Twitter, is required to explain the epidemiological dynamics over time. Overall, our results suggest that human behavior has been a key component of the outbreak propagation, and we argue that such results can lead to more efficient public health strategies specifically targeting the propagation process.
Multiomics analysis of the giant triton snail salivary gland, a crown-of-thorns starfish predator
Authors: Bose U. , Wang T. , Zhao M. , Motti C. A. , Hall M. R. , Cummins S. F. 
Published: July 2017

AbstractThe giant triton snail (Charonia tritonis) is one of the few natural predators of the adult Crown-of-Thorns starfish (COTS), a corallivore that has been damaging to many reefs in the Indo-Pacific. Charonia species have large salivary glands (SGs) that are suspected to produce either a venom and/or sulphuric acid which can immobilize their prey and neutralize the intrinsic toxic properties of COTS. To date, there is little information on the types of toxins produced by tritons. In this paper, the predatory behaviour of the C. tritonis is described. Then, the C. tritonis SG, which itself is made up of an anterior lobe (AL) and posterior lobe (PL), was analyzed using an integrated transcriptomics and proteomics approach, to identify putative toxin- and feeding-related proteins. A de novo transcriptome database and in silico protein analysis predicts that ~3800 proteins have features consistent with being secreted. A gland-specific proteomics analysis confirmed the presence of numerous SG-AL and SG-PL proteins, including those with similarity to cysteine-rich venom proteins. Sulfuric acid biosynthesis enzymes were identified, specific to the SG-PL. Our analysis of the C. tritonis SG (AL and PL) has provided a deeper insight into the biomolecular toolkit used for predation and feeding by C. tritonis.
Extensive astrocyte synchronization advances neuronal coupling in slow wave activity in vivo
Authors: Szabó Zsolt , Héja László , Szalay Gergely , Kékesi Orsolya , Füredi András , Szebényi Kornélia , Dobolyi Árpád , Orbán Tamás I. , Kolacsek Orsolya , Tompa Tamás , Miskolczy Zsombor , Biczók László , Rózsa Balázs , Sarkadi Balázs , Kardos Julianna 
Published: July 2017

AbstractSlow wave activity (SWA) is a characteristic brain oscillation in sleep and quiet wakefulness. Although the cell types contributing to SWA genesis are not yet identified, the principal role of neurons in the emergence of this essential cognitive mechanism has not been questioned. To address the possibility of astrocytic involvement in SWA, we used a transgenic rat line expressing a calcium sensitive fluorescent protein in both astrocytes and interneurons and simultaneously imaged astrocytic and neuronal activityin vivo. Here we demonstrate, for the first time, that the astrocyte network display synchronized recurrent activityin vivocoupled to UP states measured by field recording and neuronal calcium imaging. Furthermore, we present evidence that extensive synchronization of the astrocytic network precedes the spatial build-up of neuronal synchronization. The earlier extensive recruitment of astrocytes in the synchronized activity is reinforced by the observation that neurons surrounded by active astrocytes are more likely to join SWA, suggesting causality. Further supporting this notion, we demonstrate that blockade of astrocytic gap junctional communication or inhibition of astrocytic Ca2+transients reduces the ratio of both astrocytes and neurons involved in SWA. Thesein vivofindings conclusively suggest a causal role of the astrocytic syncytium in SWA generation.
A genomic glance through the fog of plasticity and diversification in Pocillopora
Authors: Johnston Erika C. , Forsman Zac H. , Flot Jean-François , Schmidt-Roach Sebastian , Pinzón Jorge H. , Knapp Ingrid S. S. , Toonen Robert J. 
Published: July 2017

AbstractScleractinian corals of the genus Pocillopora (Lamarck, 1816) are notoriously difficult to identify morphologically with considerable debate on the degree to which phenotypic plasticity, introgressive hybridization and incomplete lineage sorting obscure well-defined taxonomic lineages. Here, we used RAD-seq to resolve the phylogenetic relationships among seven species of Pocillopora represented by 15 coral holobiont metagenomic libraries. We found strong concordance between the coral holobiont datasets, reads that mapped to the Pocillopora damicornis (Linnaeus, 1758) transcriptome, nearly complete mitochondrial genomes, 430 unlinked high-quality SNPs shared across all Pocillopora taxa, and a conspecificity matrix of the holobiont dataset. These datasets also show strong concordance with previously published clustering of the mitochondrial clades based on the mtDNA open reading frame (ORF). We resolve seven clear monophyletic groups, with no evidence for introgressive hybridization among any but the most recently derived sister species. In contrast, ribosomal and histone datasets, which are most commonly used in coral phylogenies to date, were less informative and contradictory to these other datasets. These data indicate that extant Pocillopora species diversified from a common ancestral lineage within the last ~3 million years. Key to this evolutionary success story may be the high phenotypic plasticity exhibited by Pocillopora species.
The rhizosphere microbiome of burned holm-oak: potential role of the genus Arthrobacter in the recovery of burned soils
Authors: Fernández-González Antonio J. , Martínez-Hidalgo Pilar , Cobo-Díaz José F. , Villadas Pablo J. , Martínez-Molina Eustoquio , Toro Nicolás , Tringe Susannah G. , Fernández-López Manuel 
Published: July 2017

AbstractAfter a forest wildfire, the microbial communities have a transient alteration in their composition. The role of the soil microbial community in the recovery of an ecosystem following such an event remains poorly understood. Thus, it is necessary to understand the plant-microbe interactions that occur in burned soils. By high-throughput sequencing, we identified the main bacterial taxa of burnt holm-oak rhizosphere, then we obtained an isolate collection of the most abundant genus and its growth promoting activities were characterised. 16S rRNA amplicon sequencing showed that the genus Arthrobacter comprised more than 21% of the total community. 55 Arthrobacter strains were isolated and characterized using RAPDs and sequencing of the almost complete 16S rRNA gene. Our results indicate that isolated Arthrobacter strains present a very high genetic diversity, and they could play an important ecological role in interaction with the host plant by enhancing aerial growth. Most of the selected strains exhibited a great ability to degrade organic polymers in vitro as well as possibly presenting a direct mechanism for plant growth promotion. All the above data suggests that Arthrobacter can be considered as an excellent PGP rhizobacterium that may play an important role in the recovery of burned holm-oak forests.
Identification and structural characterization of LytU, a unique peptidoglycan endopeptidase from the lysostaphin family
Authors: Raulinaitis Vytas , Tossavainen Helena , Aitio Olli , Juuti Jarmo T. , Hiramatsu Keiichi , Kontinen Vesa , Permi Perttu 
Published: July 2017

AbstractWe introduce LytU, a short member of the lysostaphin family of zinc-dependent pentaglycine endopeptidases. It is a potential antimicrobial agent for S. aureus infections and its gene transcription is highly upregulated upon antibiotic treatments along with other genes involved in cell wall synthesis. We found this enzyme to be responsible for the opening of the cell wall peptidoglycan layer during cell divisions in S. aureus. LytU is anchored in the plasma membrane with the active part residing in the periplasmic space. It has a unique Ile/Lys insertion at position 151 that resides in the catalytic site-neighbouring loop and is vital for the enzymatic activity but not affecting the overall structure common to the lysostaphin family. Purified LytU lyses S. aureus cells and cleaves pentaglycine, a reaction conveniently monitored by NMR spectroscopy. Substituting the cofactor zinc ion with a copper or cobalt ion remarkably increases the rate of pentaglycine cleavage. NMR and isothermal titration calorimetry further reveal that, uniquely for its family, LytU is able to bind a second zinc ion which is coordinated by catalytic histidines and is therefore inhibitory. The pH-dependence and high affinity of binding carry further physiological implications.
Maize (Zea mays L.) genome size indicated by 180-bp knob abundance is associated with flowering time
Authors: Jian Yinqiao , Xu Cheng , Guo Zifeng , Wang Shanhong , Xu Yunbi , Zou Cheng 
Published: July 2017

AbstractFlowering time is considered one of the most important agronomic traits in maize (Zea mays L.), and previous studies have indicated that this trait is correlated with genome size. We observed a significant difference in genome size between tropical and temperate inbred lines and a moderate positive correlation between genome size and 180-bp knob abundance determined by high-throughput sequencing in maize inbred lines in this study. We assembled the reads that were mapped to 180-bp knob sequences and found that the top ten abundant 180-bp knob sequences are highly variable. Moreover, our results indicate that genome size is associated with the flowering time of both male and female flowers, in both tropical and temperate inbred lines and under both tropical and temperate environments. To identify loci associated with genome size, we performed a genome-wide association study. The analysis identified three genomic regions associated with genome size, of which two were novel while the third one is located close to the known knobs K8L1 and K8L2. Overall, our results indicate that selection for breeding materials with earlier flowering times can be assisted by choosing germplasms with smaller genome sizes and that genome size can be determined based on the abundance of 180-bp knobs.
Genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes
Authors: Jäger Susanne , Wahl Simone , Kröger Janine , Sharma Sapna , Hoffmann Per , Floegel Anna , Pischon Tobias , Prehn Cornelia , Adamski Jerzy , Müller-Nurasyid Martina , Waldenberger Melanie , Strauch Konstantin , Peters Annette , Gieger Christian , Suhre Karsten , Grallert Harald , Boeing Heiner , Schulze Matthias B. , Meidtner Karina 
Published: July 2017

AbstractDiabetes-associated metabolites may aid the identification of new risk variants for type 2 diabetes. Using targeted metabolomics within a subsample of the German EPIC-Potsdam study (n = 2500), we tested previously published SNPs for their association with diabetes-associated metabolites and conducted an additional exploratory analysis using data from the exome chip including replication within 2,692 individuals from the German KORA F4 study. We identified a total of 16 loci associated with diabetes-related metabolite traits, including one novel association between rs499974 (MOGAT2) and a diacyl-phosphatidylcholine ratio (PC aa C40:5/PC aa C38:5). Gene-based tests on all exome chip variants revealed associations betweenGFRALand PC aa C42:1/PC aa C42:0,BIN1and SM (OH) C22:2/SM C18:0 andTFRCand SM (OH) C22:2/SM C16:1). Selecting variants for gene-based tests based on functional annotation identified one additional association betweenOR51Q1and hexoses. Among single genetic variants consistently associated with diabetes-related metabolites, two (rs174550 (FADS1), rs3204953 (REV3L)) were significantly associated with type 2 diabetes in large-scale meta-analysis for type 2 diabetes. In conclusion, we identified a novel metabolite locus in single variant analyses and four genes within gene-based tests and confirmed two previously known mGWAS loci which might be relevant for the risk of type 2 diabetes.