bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathway-based subnetworks enable cross-disease biomarker discovery
Authors: Haider Syed , Yao Cindy Q. , Sabine Vicky S. , Grzadkowski Michal , Stimper Vincent , Starmans Maud H. W. , Wang Jianxin , Nguyen Francis , Moon Nathalie C. , Lin Xihui , Drake Camilla , Crozier Cheryl A. , Brookes Cassandra L. , van de Velde Cornelis J. H. , Hasenburg Annette , Kieback Dirk G. , Markopoulos Christos J. , Dirix Luc Y. , Seynaeve Caroline , Rea Daniel W. , Kasprzyk Arek , Lambin Philippe , Lio’ Pietro , Bartlett John M. S. , Boutros Paul C. 
Published: November 2018

AbstractBiomarkers lie at the heart of precision medicine. Surprisingly, while rapid genomic profiling is becoming ubiquitous, the development of biomarkers usually involves the application of bespoke techniques that cannot be directly applied to other datasets. There is an urgent need for a systematic methodology to create biologically-interpretable molecular models that robustly predict key phenotypes. Here we present SIMMS (Subnetwork Integration for Multi-Modal Signatures): an algorithm that fragments pathways into functional modules and uses these to predict phenotypes. We apply SIMMS to multiple data types across five diseases, and in each it reproducibly identifies known and novel subtypes, and makes superior predictions to the best bespoke approaches. To demonstrate its ability on a new dataset, we profile 33 genes/nodes of the PI3K pathway in 1734 FFPE breast tumors and create a four-subnetwork prediction model. This model out-performs a clinically-validated molecular test in an independent cohort of 1742 patients. SIMMS is generic and enables systematic data integration for robust biomarker discovery.
Human adipose glycerol flux is regulated by a pH gate in AQP10
Authors: Gotfryd Kamil , Mósca Andreia Filipa , Missel Julie Winkel , Truelsen Sigurd Friis , Wang Kaituo , Spulber Mariana , Krabbe Simon , Hélix-Nielsen Claus , Laforenza Umberto , Soveral Graça , Pedersen Per Amstrup , Gourdon Pontus 
Published: November 2018

AbstractObesity is a major threat to global health and metabolically associated with glycerol homeostasis. Here we demonstrate that in human adipocytes, the decreased pH observed during lipolysis (fat burning) correlates with increased glycerol release and stimulation of aquaglyceroporin AQP10. The crystal structure of human AQP10 determined at 2.3 Å resolution unveils the molecular basis for pH modulation—an exceptionally wide selectivity (ar/R) filter and a unique cytoplasmic gate. Structural and functional (in vitro and in vivo) analyses disclose a glycerol-specific pH-dependence and pinpoint pore-lining His80 as the pH-sensor. Molecular dynamics simulations indicate how gate opening is achieved. These findings unravel a unique type of aquaporin regulation important for controlling body fat mass. Thus, targeting the cytoplasmic gate to induce constitutive glycerol secretion may offer an attractive option for treating obesity and related complications.
Genotype specific pathogenicity of hepatitis E virus at the human maternal-fetal interface
Authors: Gouilly Jordi , Chen Qian , Siewiera Johan , Cartron Géraldine , Levy Claude , Dubois Martine , Al-Daccak Reem , Izopet Jacques , Jabrane-Ferrat Nabila , El Costa Hicham 
Published: November 2018

AbstractHepatitis E virus (HEV) infection, particularly HEV genotype 1 (HEV-1), can result in fulminant hepatic failure and severe placental diseases, but mechanisms underlying genotype-specific pathogenicity are unclear and appropriate models are lacking. Here, we model HEV-1 infection ex vivo at the maternal-fetal interface using the decidua basalis and fetal placenta, and compare its effects to the less-pathogenic genotype 3 (HEV-3). We demonstrate that HEV-1 replicates more efficiently than HEV-3 both in tissue explants and stromal cells, produces more infectious progeny virions and causes severe tissue alterations. HEV-1 infection dysregulates the secretion of several soluble factors. These alterations to the cytokine microenvironment correlate with viral load and contribute to the tissue damage. Collectively, this study characterizes an ex vivo model for HEV infection and provides insights into HEV-1 pathogenesis during pregnancy that are linked to high viral replication, alteration of the local secretome and induction of tissue injuries.
Neural mechanisms for learning self and other ownership
Authors: Lockwood Patricia L. , Wittmann Marco K. , Apps Matthew A. J. , Klein-Flügge Miriam C. , Crockett Molly J. , Humphreys Glyn W. , Rushworth Matthew F. S. 
Published: November 2018

AbstractSense of ownership is a ubiquitous and fundamental aspect of human cognition. Here we used model-based functional magnetic resonance imaging and a novel minimal ownership paradigm to probe the behavioural and neural mechanisms underpinning ownership acquisition for ourselves, friends and strangers. We find a self-ownership bias at multiple levels of behaviour from initial preferences to reaction times and computational learning rates. Ventromedial prefrontal cortex (vmPFC) and anterior cingulate sulcus (ACCs) responded more to self vs. stranger associations, but despite a pervasive neural bias to track self-ownership, no brain area tracked self-ownership exclusively. However, ACC gyrus (ACCg) specifically coded ownership prediction errors for strangers and ownership associative strength for friends and strangers but not for self. Core neural mechanisms for associative learning are biased to learn in reference to self but also engaged when learning in reference to others. In contrast, ACC gyrus exhibits specialization for learning about others.
Minimal memory for details in real life events
Authors: Misra Pranav , Marconi Alyssa , Peterson Matthew , Kreiman Gabriel 
Published: November 2018

AbstractThe extent to which the details of past experiences are retained or forgotten remains controversial. Some studies suggest massive storage while others describe memories as fallible summary recreations of original events. The discrepancy can be ascribed to the content of memories and how memories are evaluated. Many studies have focused on recalling lists of words/pictures, which lack the critical ingredients of real world memories. Here we quantified the ability to remember details about one hour of real life. We recorded video and eye movements while subjects walked along specified routes and evaluated whether they could distinguish video clips from their own experience from foils. Subjects were minimally above chance in remembering the minutiae of their experiences. Recognition of specific events could be partly explained by a machine-learning model of video contents. These results quantify recognition memory for events in real life and show that the details of everyday experience are largely not retained in memory.
Cyclosporine A binding to COX-2 reveals a novel signaling pathway that activates the IRE1α unfolded protein response sensor
Authors: Groenendyk Jody , Paskevicius Tautvydas , Urra Hery , Viricel Clement , Wang Kui , Barakat Khaled , Hetz Claudio , Kurgan Lukasz , Agellon Luis B. , Michalak Marek 
Published: November 2018

AbstractCyclosporine, a widely used immunosuppressant in organ transplantation and in treatment of various autoimmune diseases, activates the unfolded protein response (UPR), an ER stress coping response. In this study we discovered a new and unanticipated cyclosporine-dependent signaling pathway, with cyclosporine triggering direct activation of the UPR. COX-2 binds to and activates IRE1α, leading to IRE1α splicing of XBP1 mRNA. Molecular interaction and modeling analyses identified a novel interaction site for cyclosporine with COX-2 which caused enhancement of COX-2 enzymatic activity required for activation of the IRE1α branch of the UPR. Cyclosporine-dependent activation of COX-2 and IRE1α in mice indicated that cyclosporine-COX-2-IRE1α signaling pathway was functional in vivo. These findings identify COX-2 as a new IRE1α binding partner and regulator of the IRE1α branch of the UPR pathway, and establishes the mechanism underlying cytotoxicity associated with chronic cyclosporine exposure.
Enhanced EPR directed and Imaging guided Photothermal Therapy using Vitamin E Modified Toco-Photoxil
Authors: Chauhan Deepak S. , Bukhari Amirali B. , Ravichandran Gayathri , Gupta Ramkrishn , George Liya , Poojari Radhika , Ingle Aravind , Rengan Aravind K. , Shanavas Asifkhan , Srivastava Rohit , De Abhijit 
Published: November 2018

AbstractHerein we report synthesis, characterization and preclinical applications of a novel hybrid nanomaterial Toco-Photoxil developed using vitamin E modified gold coated poly (lactic-co-glycolic acid) nanoshells incorporating Pgp inhibitor d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a highly inert and disintegrable photothermal therapy (PTT) agent. Toco-Photoxil is highly biocompatible, physiologically stable PTT material with an average diameter of 130 nm that shows good passive accumulation (2.3% ID) in solid tumors when delivered systemically. In comparison to its surface modified counterparts such as IR780-Toco-Photoxil, FA-Toco-Photoxil or FA-IR780-Toco-Photoxil accumulation are merely ~0.3% ID, ~0.025% ID and ~0.005% ID in folate receptor (FR) negative and positive tumor model. Further, Toco-Photoxil variants are prepared by tuning the material absorbance either at 750 nm (narrow) or 915 nm (broad) to study optimal therapeutic efficacy in terms of peak broadness and nanomaterial’s concentration. Our findings suggest that Toco-Photoxil tuned at 750 nm absorbance is more efficient (P = 0.0097) in preclinical setting. Toco-Photoxil shows complete passiveness in critical biocompatibility test and reasonable body clearance. High tumor specific accumulation from systemic circulation, strong photothermal conversion and a very safe material property in body physiology makes Toco-Photoxil a superior and powerful PTT agent, which may pave its way for fast track clinical trial in future.
Acute alcohol administration dampens central extended amygdala reactivity
Authors: Hur Juyoen , Kaplan Claire M. , Smith Jason F. , Bradford Daniel E. , Fox Andrew S. , Curtin John J. , Shackman Alexander J. 
Published: November 2018

AbstractAlcohol use is common, imposes a staggering burden on public health, and often resists treatment. The central extended amygdala (EAc)—including the bed nucleus of the stria terminalis (BST) and the central nucleus of the amygdala (Ce)—plays a key role in prominent neuroscientific models of alcohol drinking, but the relevance of these regions to acute alcohol consumption in humans remains poorly understood. Using a single-blind, randomized-groups design, multiband fMRI data were acquired from 49 social drinkers while they performed a well-established emotional faces paradigm after consuming either alcohol or placebo. Relative to placebo, alcohol significantly dampened reactivity to emotional faces in the BST. To rigorously assess potential regional differences in activation, data were extracted from unbiased, anatomically predefined regions of interest. Analyses revealed similar levels of dampening in the BST and Ce. In short, alcohol transiently reduces reactivity to emotional faces and it does so similarly across the two major divisions of the human EAc. These observations reinforce the translational relevance of addiction models derived from preclinical work in rodents and provide new insights into the neural systems most relevant to the consumption of alcohol and to the initial development of alcohol abuse in humans.
Audit of stored strain energy and extent of future earthquake rupture in central Himalaya
Authors: Sreejith K. M. , Sunil P. S. , Agrawal Ritesh , Saji Ajish P. , Rajawat A. S. , Ramesh D. S. 
Published: November 2018

AbstractThe deadly 25 April 2015 Gorkha earthquake (Mw = 7.8) and aftershocks have partially released the accumulated interseismic strain along the Main Himalayan Thrust (MHT). Postseismic deformation associated with this earthquake is mainly confined to the north of the rupture. This suggests possible occurrence of future large events towards west or south, where MHT is locked. Asperities arising due to heterogeneity in the stress-strain patterns are believed to play a major role in controlling the coseismic rupture propagation. We determine interseismic coupling along the MHT and spatial variations in total strain rate using two decades of GPS, InSAR and sprit leveling data. Further, b-values derived from the seismicity data are used to identify zones of stress accumulation. We demonstrate that the 2015 earthquake ruptured an asperity which hosted high strain and stress accumulation prior to the event. A similar asperity towards west of the epicenter with unreleased strain energy is identified. This could spawn a future large earthquake akin in magnitude to the 2015 Gorkha event. These findings compel a revisit of the seismic hazard assessment of the central Himalaya.
Unprecedented rains decimate surface microbial communities in the hyperarid core of the Atacama Desert
Authors: Azua-Bustos A. , Fairén A. G. , González-Silva C. , Ascaso C. , Carrizo D. , Fernández-Martínez M. Á. , Fernández-Sampedro M. , García-Descalzo L. , García-Villadangos M. , Martin-Redondo M. P. , Sánchez-García L. , Wierzchos J. , Parro V. 
Published: November 2018

AbstractThe hyperarid core of the Atacama Desert, the driest and oldest desert on Earth, has experienced a number of highly unusual rain events over the past three years, resulting in the formation of previously unrecorded hypersaline lagoons, which have lasted several months. We have systematically analyzed the evolution of the lagoons to provide quantitative field constraints of large-scale impacts of the rains on the local microbial communities. Here we show that the sudden and massive input of water in regions that have remained hyperarid for millions of years is harmful for most of the surface soil microbial species, which are exquisitely adapted to survive with meager amounts of liquid water, and quickly perish from osmotic shock when water becomes suddenly abundant. We found that only a handful of bacteria, remarkably a newly identified species of Halomonas, remain metabolically active and are still able to reproduce in the lagoons, while no archaea or eukaryotes were identified. Our results show that the already low microbial biodiversity of extreme arid regions greatly diminishes when water is supplied quickly and in great volumes. We conclude placing our findings in the context of the astrobiological exploration of Mars, a hyperarid planet that experienced catastrophic floodings in ancient times.
A Lateral Flow Immunochromato-graphic Strip Test for Rapid Detection of Oseltamivir Phosphate in Egg and Chicken Meat
Authors: Yang Xingdong , Yang Jifei , Wang Yinbiao , Li Lili , Sun Zhongke , Yue Zonghao , Tian Fengshou , He Le , Hu Xiaofei 
Published: November 2018

AbstractA lateral flow immunochromatographic strip test (LFIST) based on a competitive format was developed for rapid and sensitive on-site detection of oseltamivir phosphate (OP) residues in poultry product. The sensitivity (half inhibitory concentration, IC50) of the LFIST in the detection of egg and chicken meat samples was confirmed to be 2.56 and 2.63 µg/kg, and the limit detection (LOD) value were 0.43 and 0.42 µg/kg, respectively. For intra-assay and inter-assay reproducibility, recoveries of OP spiked samples ranged between 82.8% and 91.2% with coefficients of variations (CV) less than 5.67% (intra-assay) and 6.52% (inter-assay). The performance of LFIST was comparable to high-performance liquid chromatography (HPLC) in a parallel testing of egg samples and chicken samples. LFIST takes less than 5 minutes, eliminates the dependency on professional personnel, and thus can be used as a surveillance tool for on-site detection of OP residues.
Modulation of salivary cytokines in response to alcohol, tobacco and caffeine consumption: a pilot study
Authors: Sheth Chirag C. , López-Pedrajas Rosa M. , Jovani-Sancho Maria del Mar , González-Martínez Raquel , Veses Veronica 
Published: November 2018

AbstractIt has been shown that long-term stimulant consumption alters the biological and microbiological status of the oral cavity. We present a pilot study describing stimulant-specific oral immunomodulation in the oral cavity. Changes in salivary cytokine levels in response to long-term alcohol, tobacco and caffeine were identified. Volunteers were recruited from amongst the patients visiting University Dental Clinic of CEU Cardenal Herrera University (Alfara del Patriarca, Spain). Participants were grouped according to their self-reported levels of consumption of either caffeine, alcohol or tobacco (control group volunteers were non-consumers of all three). Informed consent was provided and stimulated saliva samples were obtained and assayed for interleukin-1α IL-1α), Tumor Necrosis Factor α (TNF-α) and Interferon γ IFN-γ). Long-term, high-level consumers of alcohol or tobacco exhibited elevated salivary concentrations of the three inflammatory cytokines with respect to control values. Specifically, IL-1α was found to be elevated in alcohol users whilst IFN-γ concentration higher in tobacco users versus controls. Long-term caffeine consumers displayed elevated levels of IFN-γ and TNF-α, whereas IL-1α levels were reduced with respect to control volunteers. This pilot study demonstrates that salivary cytokines can be modulated in response to quantity and duration of alcohol, caffeine or tobacco consumption.
Investigation of the Roles of Plasma Species Generated by Surface Dielectric Barrier Discharge
Authors: Pai Kedar , Timmons Chris , Roehm Kevin D. , Ngo Alvin , Narayanan Sai Sankara , Ramachandran Akhilesh , Jacob Jamey D. , Ma Li Maria , Madihally Sundararajan V. 
Published: November 2018

AbstractAs an emerging sterilization technology, cold atmospheric plasma offers a dry, non-thermal, rapid process that is minimally damaging to a majority of substrates. However, the mechanisms by which plasma interacts with living cells are poorly understood and the plasma generation apparatuses are complex and resource-intensive. In this study, the roles of reactive oxygen species (ROS), nitric oxide (NO), and charged particles (ions) produced by surface dielectric barrier discharge (SDBD) plasma on prokaryotic (Listeria monocytogenes (Gram-positive)) and eukaryotic (human umbilical vein endothelial cells (HUVEC)) cellular function were evaluated. HUVEC and bacterial oxidative stress responses, the accumulation of nitrite in aqueous media, air ion density, and bacterial inactivation at various distances from SDBD actuators were measured. SDBD actuator designs were also varied in terms of electrode number and length to evaluate the cellular effects of plasma volume and power distribution. NO and ions were found to contribute minimally to the observed cellular effects, whereas ROS were found to cause rapid bacterial inactivation, induce eukaryotic and prokaryotic oxidative stress, and result in rapid oxidation of bovine muscle tissue. The results of this study underscore the dominance of ROS as the major plasma generated species responsible for cellular effects, with ions and RNS having a secondary, complimentary role.
Adult Antarctic krill proves resilient in a simulated high CO2 ocean
Authors: Ericson Jessica. A. , Hellessey Nicole , Kawaguchi So , Nicol Stephen , Nichols Peter D. , Hoem Nils , Virtue Patti 
Published: November 2018

AbstractAntarctic krill (Euphausia superba) have a keystone role in the Southern Ocean, as the primary prey of Antarctic predators. Decreases in krill abundance could result in a major ecological regime shift, but there is limited information on how climate change may affect krill. Increasing anthropogenic carbon dioxide (CO2) emissions are causing ocean acidification, as absorption of atmospheric CO2 in seawater alters ocean chemistry. Ocean acidification increases mortality and negatively affects physiological functioning in some marine invertebrates, and is predicted to occur most rapidly at high latitudes. Here we show that, in the laboratory, adult krill are able to survive, grow, store fat, mature, and maintain respiration rates when exposed to near-future ocean acidification (1000–2000 μatm pCO2) for one year. Despite differences in seawater pCO2 incubation conditions, adult krill are able to actively maintain the acid-base balance of their body fluids in near-future pCO2, which enhances their resilience to ocean acidification.
Biomineralization of calcium phosphate revealed by in situ liquid-phase electron microscopy
Authors: Wang Xiaoyue , Yang Jie , Andrei Carmen M. , Soleymani Leyla , Grandfield Kathryn 
Published: November 2018

AbstractCalcium phosphate biomineralization is essential to the formation of bones and teeth, and other pathological calcifications. Unravelling the mechanism of calcium phosphate nucleation and growth contributes significantly to understanding diseases caused by pathological mineralization, and also to designing biomimetic materials with suitable properties. Recently, calcium phosphate was proposed to mineralize following a non-classical crystal growth pathway of pre-nucleation cluster aggregation. Liquid-phase transmission electron microscopy allows dynamic processes to be recorded continuously inside liquid. Here we present direct evidence, based on continuous monitoring in liquid, to confirm that calcium phosphate mineralization from simulated body fluid occurs by particle attachment, shown with nanoscale spatial resolution and sufficient temporal resolution. This work may lay the foundation for future investigation of mineralization in other relevant biological systems in humans and vertebrates.
Comprehensive transcriptome analysis of Sarcophaga peregrina, a forensically important fly species
Authors: Kim Ji Yeon , Lim Hye Young , Shin Sang Eon , Cha Hyo Kyeong , Seo Jeong-Han , Kim Suel-Kee , Park Seong Hwan , Son Gi Hoon 
Published: November 2018

AbstractSarcophaga peregrina (flesh fly) is a frequently found fly species in Palaearctic, Oriental, and Australasian regions that can be used to estimate minimal postmortem intervals important for forensic investigations. Despite its forensic importance, the genome information of S. peregrina has not been fully described. Therefore, we generated a comprehensive gene expression dataset using RNA sequencing and carried out de novo assembly to characterize the S. peregrina transcriptome. We obtained precise sequence information for RNA transcripts using two different methods. Based on primary sequence information, we identified sets of assembled unigenes and predicted coding sequences. Functional annotation of the aligned unigenes was performed using the UniProt, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes databases. As a result, 26,580,352 and 83,221 raw reads were obtained using the Illumina MiSeq and Pacbio RS II Iso-Seq sequencing applications, respectively. From these reads, 55,730 contigs were successfully annotated. The present study provides the resulting genome information of S. peregrina, which is valuable for forensic applications.