bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the informativeness of deep learning annotations for human complex diseases
Authors: Dey Kushal K. , van de Geijn Bryce , Kim Samuel Sungil , Hormozdiari Farhad , Kelley David R. , Price Alkes L. 
Published: September 2020

AbstractDeep learning models have shown great promise in predicting regulatory effects from DNA sequence, but their informativeness for human complex diseases is not fully understood. Here, we evaluate genome-wide SNP annotations from two previous deep learning models, DeepSEA and Basenji, by applying stratified LD score regression to 41 diseases and traits (average N = 320K), conditioning on a broad set of coding, conserved and regulatory annotations. We aggregated annotations across all (respectively blood or brain) tissues/cell-types in meta-analyses across all (respectively 11 blood or 8 brain) traits. The annotations were highly enriched for disease heritability, but produced only limited conditionally significant results: non-tissue-specific and brain-specific Basenji-H3K4me3 for all traits and brain traits respectively. We conclude that deep learning models have yet to achieve their full potential to provide considerable unique information for complex disease, and that their conditional informativeness for disease cannot be inferred from their accuracy in predicting regulatory annotations.
Pressure-stabilized divalent ozonide CaO3 and its impact on Earth’s oxygen cycles
Authors: Wang Yanchao , Xu Meiling , Yang Liuxiang , Yan Bingmin , Qin Qin , Shao Xuecheng , Zhang Yunwei , Huang Dajian , Lin Xiaohuan , Lv Jian , Zhang Dongzhou , Gou Huiyang , Mao Ho-kwang , Chen Changfeng , Ma Yanming 
Published: September 2020

AbstractHigh pressure can drastically alter chemical bonding and produce exotic compounds that defy conventional wisdom. Especially significant are compounds pertaining to oxygen cycles inside Earth, which hold key to understanding major geological events that impact the environment essential to life on Earth. Here we report the discovery of pressure-stabilized divalent ozonide CaO3 crystal that exhibits intriguing bonding and oxidation states with profound geological implications. Our computational study identifies a crystalline phase of CaO3 by reaction of CaO and O2 at high pressure and high temperature conditions; ensuing experiments synthesize this rare compound under compression in a diamond anvil cell with laser heating. High-pressure x-ray diffraction data show that CaO3 crystal forms at 35 GPa and persists down to 20 GPa on decompression. Analysis of charge states reveals a formal oxidation state of −2 for ozone anions in CaO3. These findings unravel the ozonide chemistry at high pressure and offer insights for elucidating prominent seismic anomalies and oxygen cycles in Earth’s interior. We further predict multiple reactions producing CaO3 by geologically abundant mineral precursors at various depths in Earth’s mantle.
In vitro hyperthermic effect of magnetic fluid on cervical and breast cancer cells
Authors: Bhardwaj Anand , Parekh Kinnari , Jain Neeraj 
Published: September 2020

AbstractSelf-regulating temperature-controlled nanoparticles such as Mn–Zn ferrite nanoparticles based magnetic fluid can be a better choice for magnetic fluid hyperthermia because of its controlled regulation of hyperthermia temperature window of 43–45 °C. To test this hypothesis magnetic fluid with said properties was synthesized, and its effect on cervical and breast cancer cell death was studied. We found that the hyperthermia window of 43–45 °C was maintained for one hour at the smallest possible concentration of 0.35 mg/mL without altering the magnetic field applicator parameters. Their hyperthermic effect on HeLa and MCF7 was investigated at the magnetic field of 15.3 kA/m and frequency 330 kHz, which is close to the upper safety limit of 5 * 109 A/m s. We have tested the cytotoxicity of synthesized Mn–Zn ferrite fluid using MTT assay and the results were validated by trypan blue dye exclusion assay that provides the naked eye microscopic view of actual cell death. Since cancer cells tend to resist treatment and show re-growth, we also looked into the effect of multiple sessions hyperthermia using a 24 h window till 72 h using trypan blue assay. The multiple sessions of hyperthermia showed promising results, and it indicated that a minimum of 3 sessions, each of one-hour duration, is required for the complete killing of cancer cells. Moreover, to simulate an in vivo cellular environment, a phantom consisting of magnetic nanoparticles dispersed in 1 and 5% agarose gel was constituted and studied. These results will help to decide the magnetic fluid based hyperthermic therapeutic strategies using temperature-sensitive magnetic fluid.
Multilevel structural evaluation of signed directed social networks based on balance theory
Authors: Aref Samin , Dinh Ly , Rezapour Rezvaneh , Diesner Jana 
Published: September 2020

AbstractBalance theory explains how network structural configurations relate to tension in social systems, which are commonly modeled as static undirected signed graphs. We expand this modeling approach by incorporating directionality of edges and considering three levels of analysis for balance assessment: triads, subgroups, and the whole network. For triad-level balance, we develop a new measure by utilizing semicycles that satisfy the condition of transitivity. For subgroup-level balance, we propose measures of cohesiveness (intra-group solidarity) and divisiveness (inter-group antagonism) to capture balance within and among subgroups. For network-level balance, we re-purpose the normalized line index to incorporate directionality and assess balance based on the proportion of edges whose position suits balance. Through comprehensive computational analyses, we quantify, analyze, and compare patterns of social structure in triads, subgroups, and the whole network across a range of social settings. We then apply our multilevel framework to examine balance in temporal and multilayer networks to demonstrates the generalizability of our approach. In most cases, we find relatively high balance across the three levels; providing another confirmation of balance theory. We also deliver empirical evidence for the argument that balance at different levels is not the same social phenomenon measured at different scales, but represents different properties (triadic balance, internal cohesion and external division of subgroups, and overall network polarization), and should therefore be evaluated independently from one another. We propose a comprehensive yet parsimonious approach to address this need.
Downregulation of the CCL2/CCR2 and CXCL10/CXCR3 axes contributes to antitumor effects in a mouse model of malignant glioma
Authors: Shono Kenji , Yamaguchi Izumi , Mizobuchi Yoshifumi , Kagusa Hiroshi , Sumi Akiko , Fujihara Toshitaka , Nakajima Kohei , Kitazato Keiko T. , Matsuzaki Kazuhito , Saya Hideyuki , Takagi Yasushi 
Published: September 2020

AbstractGlioblastoma multiforme involves glioma stem cells (GSCs) that are resistant to various therapeutic approaches. Here, we studied the importance of paracrine signaling in the glioma microenvironment by focusing on the celecoxib-mediated role of chemokines C–C motif ligand 2 (CCL2), C-X-C ligand 10 (CXCL10), and their receptors, CCR2 and CXCR3, in GSCs and a GSC-bearing malignant glioma model. C57BL/6 mice were injected with orthotopic GSCs intracranially and divided into groups administered either 10 or 30 mg/kg celecoxib, or saline to examine the antitumor effects associated with chemokine expression. In GSCs, we analyzed cell viability and expression of chemokines and their receptors in the presence/absence of celecoxib. In the malignant glioma model, celecoxib exhibited antitumor effects in a dose dependent manner and decreased protein and mRNA levels of Ccl2 and CxcL10 and Cxcr3 but not of Ccr2. CCL2 and CXCL10 co-localized with Nestin+ stem cells, CD16+ or CD163+ macrophages and Iba-1+ microglia. In GSCs, celecoxib inhibited Ccl2 and Cxcr3 expression in a nuclear factor-kappa B-dependent manner but not Ccr2 and CxcL10. Moreover, Ccl2 silencing resulted in decreased GSC viability. These results suggest that celecoxib-mediated regulation of the CCL2/CCR2 and CXCL10/ CXCR3 axes may partially contribute to glioma-specific antitumor effects.
Changes in subclass-specific IgG Fc glycosylation associated with the postnatal maturation of the murine immune system
Authors: Barrientos Gabriela , Habazin Siniša , Novokmet Mislav , Almousa Yahia , Lauc Gordan , Conrad Melanie L. 
Published: September 2020

AbstractEarly postnatal life is characterized by a critical time period in which the developing neonatal immune system transitions from passive immunity, induced by protective maternal antibodies, to the competence of a fully functioning immune system. The inflammatory capability of both maternal and neonatal antibodies is governed by N-linked glycosylation of the Fc region, and though this has been examined extensively in adults, there is currently little information regarding antibody glycosylation patterns during early postnatal life. To characterize the murine IgG Fc glycosylation profile during early life, we used nano-LC-ESI-Qq-TOF mass spectrometry analysis to assess subclass specific Asn-297 glycosylation patterns in the serum of BALB/c mice from 5–60 days of age. From birth to adulthood, we observed a decline in proinflammatory Fc glycosylation in all IgG subclasses. This was shown by significantly reduced agalactosylated and monogalactosylated structures combined with increased sialylation after weaning at 45 and 60 days of age. This information indicates that the transition between neonatal life and adulthood in mice is accompanied by reduction of inflammatory IgG antibodies. Our study contributes to a growing body of literature indicating the importance of IgG Fc glycosylation and its association with inflammation during different life stages.
Prolonged ursodeoxycholic acid administration reduces acute ischaemia-induced arrhythmias in adult rat hearts
Authors: Ferraro Elisa , Pozhidaeva Lidia , Pitcher David S. , Mansfield Catherine , Koh Jia Han Benjamin , Williamson Catherine , Aslanidi Oleg , Gorelik Julia , Ng Fu Siong 
Published: September 2020

AbstractAcute myocardial ischaemia and reperfusion (I–R) are major causes of ventricular arrhythmias in patients with a history of coronary artery disease. Ursodeoxycholic acid (UDCA) has previously been shown to be antiarrhythmic in fetal hearts. This study was performed to investigate if UDCA protects against ischaemia-induced and reperfusion-induced arrhythmias in the adult myocardium, and compares the effect of acute (perfusion only) versus prolonged (2 weeks pre-treatment plus perfusion) UDCA administration. Langendorff-perfused adult Sprague–Dawley rat hearts were subjected to acute regional ischaemia by ligation of the left anterior descending artery (10 min), followed by reperfusion (2 min), and arrhythmia incidence quantified. Prolonged UDCA administration reduced the incidence of acute ischaemia-induced arrhythmias (p = 0.028), with a reduction in number of ventricular ectopic beats during the ischaemic phase compared with acute treatment (10 ± 3 vs 58 ± 15, p = 0.036). No antiarrhythmic effect was observed in the acute UDCA administration group. Neither acute nor prolonged UDCA treatment altered the incidence of reperfusion arrhythmias. The antiarrhythmic effect of UDCA may be partially mediated by an increase in cardiac wavelength, due to the attenuation of conduction velocity slowing (p = 0.03), and the preservation of Connexin43 phosphorylation during acute ischaemia (p = 0.0027). The potential antiarrhythmic effects of prolonged UDCA administration merit further investigation.
Anomalous tensile response of bacterial cellulose nanopaper at intermediate strain rates
Authors: Santmarti Alba , Liu Hon Wah , Herrera Natalia , Lee Koon-Yang 
Published: September 2020

AbstractNanocellulose network in the form of cellulose nanopaper is an important material structure and its time-dependent mechanical response is crucial in many of its potential applications. In this work, we report the influences of grammage and strain rate on the tensile response of bacterial cellulose (BC) nanopaper. BC nanopaper with grammages of 20, 40, 60 and 80 g m−2 were tested in tension at strain rates ranging from 0.1% s−1 to 50% s−1. At strain rates $$\le$$
≤
2.5% s−1, both the tensile modulus and strength of the BC nanopapers stayed constant at ~ 14 GPa and ~ 120 MPa, respectively. At higher strain rates of 25% s−1 and 50% s−1 however, the tensile properties of the BC nanopapers decreased significantly. This observed anomalous tensile response of BC nanopaper is attributed to inertial effect, in which some of the curled BC nanofibres within the nanopaper structure do not have enough time to uncurl before failure at such high strain rates. Our measurements further showed that BC nanopaper showed little deformation under creep, with a secondary creep rate of only ~ 10–6 s−1. This stems from the highly crystalline nature of BC, as well as the large number of contact or physical crosslinking points between adjacent BC nanofibres, further reducing the mobility of the BC nanofibres in the nanopaper structure.
Nonlinear dynamic analysis of the pure “buckling” mechanism during blow-out trauma of the human orbit
Authors: Zmuda Trzebiatowski Marcin Adam , Kłosowski Paweł , Skorek Andrzej , Żerdzicki Krzysztof , Lemski Paweł , Koberda Mateusz 
Published: September 2020

AbstractConsidering the interplay between orbital bones and intraorbital soft tissues, commonly accepted patterns of the blow-out type of trauma within the human orbit require more thorough investigation to assess the minimal health-threatening impact value. Two different three-dimensional finite element method (FEM) models of the human orbital region were developed to simulate the pure “buckling” mechanism of orbital wall fracture in two variants: the model of orbital bone elements and the model of orbital bone, orbit and intraorbital tissue elements. The mechanical properties of the so-defined numerical skull fragment were applied to the model according to the unique laboratory tensile stress tests performed on small and fragile specimens of orbital bones as well as using the data available in the literature. The nonlinear transient analysis of the contact problem between bodies that differ substantially in terms of the Young’s modulus was carried out to investigate the interaction of different bodies within an instant injury. Potential damage areas were found within the lower orbital wall as well as the destructive load values for both FEM skull models (7,660 N and 8,520 N). Moreover, numerical simulations were validated by comparing them with computed tomography scans of real injuries.
Characterization of raffinose metabolism genes uncovers a wild Arachis galactinol synthase conferring tolerance to abiotic stresses
Authors: Vinson Christina C. , Mota Ana P. Z. , Porto Brenda N. , Oliveira Thais N. , Sampaio Iracyara , Lacerda Ana L. , Danchin Etienne G. J. , Guimaraes Patricia M. , Williams Thomas C. R. , Brasileiro Ana C. M. 
Published: September 2020

AbstractRaffinose family oligosaccharides (RFOs) are implicated in plant regulatory mechanisms of abiotic stresses tolerance and, despite their antinutritional proprieties in grain legumes, little information is available about the enzymes involved in RFO metabolism in Fabaceae species. In the present study, the systematic survey of legume proteins belonging to five key enzymes involved in the metabolism of RFOs (galactinol synthase, raffinose synthase, stachyose synthase, alpha-galactosidase, and beta-fructofuranosidase) identified 28 coding-genes in Arachis duranensis and 31 in A. ipaënsis. Their phylogenetic relationships, gene structures, protein domains, and chromosome distribution patterns were also determined. Based on the expression profiling of these genes under water deficit treatments, a galactinol synthase candidate gene (AdGolS3) was identified in A. duranensis. Transgenic Arabidopsis plants overexpressing AdGolS3 exhibited increased levels of raffinose and reduced stress symptoms under drought, osmotic, and salt stresses. Metabolite and expression profiling suggested that AdGolS3 overexpression was associated with fewer metabolic perturbations under drought stress, together with better protection against oxidative damage. Overall, this study enabled the identification of a promising GolS candidate gene for metabolic engineering of sugars to improve abiotic stress tolerance in crops, whilst also contributing to the understanding of RFO metabolism in legume species.
Early origin and global colonisation of foot-and-mouth disease virus
Authors: Aiewsakun Pakorn , Pamornchainavakul Nakarin , Inchaisri Chaidate 
Published: September 2020

AbstractIn this study, we compiled 84-year worth (1934–2017) of genomic and epidemiological data of foot-and-mouth disease virus (FMDV), and performed comprehensive analyses to determine its early origin and transmission route. We found that recombination is a key feature of FMDV, and that the genomic regions coding for structural and non-structural proteins have markedly different evolutionary histories, and evolve at different rates. Despite all of these differences, analyses of both structural and non-structural protein coding regions consistently suggested that the most recent common ancestor of FMDV could be dated back to the Middle Age, ~ 200 to 300 years earlier than previously thought. The ancestors of the Euro-Asiatic and SAT strains could be dated back to the mid-seventeenth century, and to the mid-fifteenth to mid-sixteenth century, respectively. Our results implicated Mediterranean counties as an early geographical origin of FMDV before spreading to Europe and subsequently to Asia and South America.
Polymerization shrinkage behaviour of resin composites functionalized with unsilanized bioactive glass fillers
Authors: Par Matej , Mohn Dirk , Attin Thomas , Tarle Zrinka , Tauböck Tobias T. 
Published: September 2020

AbstractPrevious work has shown that partial replacement of reinforcing fillers with unsilanized silica particles can diminish polymerization shrinkage stress of dental resin composites. The aim of the present study was to investigate whether such an effect can be attained by using unsilanized bioactive glass (BG). Incorporating BG fillers into resin composites is interesting due to their potential for exerting caries-preventive effects. Experimental light-curable composites with a total filler load of 77 wt% were prepared. Reinforcing fillers were partially replaced with 0–60 wt% of BG 45S5 and an experimental low-sodium fluoride-containing BG. The following properties were investigated: linear shrinkage, degree of conversion, shrinkage stress, maximum shrinkage stress rate, and time to achieve maximum shrinkage stress rate. The diminishing effect of BG 45S5 on shrinkage stress was mediated by a decrease in degree of conversion caused by this BG type. In contrast, as the degree of conversion remained unaffected by the experimental BG, the resulting shrinkage behaviour was governed by the effect of varying amounts of silanized and unsilanized fillers on material’s viscoelastic properties. The replacement of silanized reinforcing fillers with unsilanized BG did not reduce polymerization shrinkage stress unless the reduction was attained indirectly through a diminished degree of conversion.
Single-cell RNA-seq identifies unique transcriptional landscapes of human nucleus pulposus and annulus fibrosus cells
Authors: Fernandes Lorenzo M. , Khan Nazir M. , Trochez Camila M. , Duan Meixue , Diaz-Hernandez Martha E. , Presciutti Steven M. , Gibson Greg , Drissi Hicham 
Published: September 2020

AbstractIntervertebral disc (IVD) disease (IDD) is a complex, multifactorial disease. While various aspects of IDD progression have been reported, the underlying molecular pathways and transcriptional networks that govern the maintenance of healthy nucleus pulposus (NP) and annulus fibrosus (AF) have not been fully elucidated. We defined the transcriptome map of healthy human IVD by performing single-cell RNA-sequencing (scRNA-seq) in primary AF and NP cells isolated from non-degenerated lumbar disc. Our systematic and comprehensive analyses revealed distinct genetic architecture of human NP and AF compartments and identified 2,196 differentially expressed genes. Gene enrichment analysis showed that SFRP1, BIRC5, CYTL1, ESM1 and CCNB2 genes were highly expressed in the AF cells; whereas, COL2A1, DSC3, COL9A3, COL11A1, and ANGPTL7 were mostly expressed in the NP cells. Further, functional annotation clustering analysis revealed the enrichment of receptor signaling pathways genes in AF cells, while NP cells showed high expression of genes related to the protein synthesis machinery. Subsequent interaction network analysis revealed a structured network of extracellular matrix genes in NP compartments. Our regulatory network analysis identified FOXM1 and KDM4E as signature transcription factor of AF and NP respectively, which might be involved in the regulation of core genes of AF and NP transcriptome.
Expression and functional analysis of the nobiletin biosynthesis-related gene CitOMT in citrus fruit
Authors: Seoka Mao , Ma Gang , Zhang Lancui , Yahata Masaki , Yamawaki Kazuki , Kan Toshiyuki , Kato Masaya 
Published: September 2020

AbstractNobiletin, a polymethoxy flavone (PMF), is specific to citrus and has been reported to exhibit important health-supporting properties. Nobiletin has six methoxy groups at the 3′,4′,5,6,7,8-positions, which are catalyzed by O-methyltransferases (OMTs). To date, researches on OMTs in citrus fruit are still limited. In the present study, a novel OMT gene (CitOMT) was isolated from two citrus varieties Satsuma mandarin (Citrus unshiu Marc.) and Ponkan mandarin (Citrus reticulata Blanco), and its function was characterized in vitro. The results showed that the expression of CitOMT in the flavedo of Ponkan mandarin was much higher than that of Satsuma mandarin during maturation, which was consistent with the higher accumulation of nobiletin in Ponkan mandarin. In addition, functional analysis showed that the recombinant protein of CitOMT had methylation activity to transfer a methyl group to 3′-hydroxy group of flavones in vitro. Because methylation at the 3′-position of flavones is vital for the nobiletin biosynthesis, CitOMT may be a key gene responsible for nobiletin biosynthesis in citrus fruit. The results presented in this study will provide new strategies to enhance nobiletin accumulation and improve the nutritional qualities of citrus fruit.