bluuebunny/crossref_metadata_2025_split huggingface dataset:
The first complete genomic sequences of African swine fever virus isolated in Poland
Authors: Mazur-Panasiuk Natalia , Woźniakowski Grzegorz , Niemczuk Krzysztof 
Published: March 2019

AbstractAfrican swine fever (ASF) is a contagious, notifiable viral disease, which is considered a significant threat not only for European, but also for worldwide pork production, since recently the virus emerged within numerous Chinese pig herds. The disease was introduced in Poland in 2014 and up to the end of 2018, 213 outbreaks in pigs and 3347 cases in wild boars have been reported. The presented study describes the whole genome sequencing of seven Polish isolates, collected between 2016 and 2017, using next generation sequencing (NGS) technology. The complete, genomic sequences of these isolates were compared against five other closely related ASFV genomes, annotated in the NCBI database. The obtained sequences were from 189.393 to 189.405 bp long and encoded 187–190 open reading frames (ORFs). The isolates were grouped within genotype II and showed 99.941 to 99.956% nucleotide identity to the Georgia 2007/1 reference strain.
The Significance of the Effect of Visceral Adiposity on Left Ventricular Diastolic Function in the General Population
Authors: Sawada Naoko , Daimon Masao , Kawata Takayuki , Nakao Tomoko , Kimura Koichi , Nakanishi Koki , Kurano Makoto , Hirokawa Megumi , Xu Boqing , Yamanaka Yuko , Kato Tomoko S. , Watanabe Masafumi , Yatomi Yutaka , Komuro Issei 
Published: March 2019

AbstractWe evaluated the association between visceral adiposity and left ventricular (LV) diastolic function in association with plasma adiponectin levels in 213 subjects without overt cardiac diseases. Abdominal visceral fat area was quantified by computed tomography. Excessive visceral fat was significantly associated with impaired diastolic parameters including E/A, E′ and E/E′. Although serum adiponectin levels decreased with increased visceral adiposity, there was no independent association between serum adiponectin levels and diastolic parameters, which suggest that the role of adiponectin in this association might be indirect.
Integrative analysis of KIF4A, 9, 18A, and 23 and their clinical significance in low-grade glioma and glioblastoma
Authors: Cho Sang Yeon , Kim Sungha , Kim Gwanghun , Singh Parul , Kim Dong Woon 
Published: March 2019

AbstractTo determine the prognostic significance of kinesin superfamily gene (KIF) expression in patients with brain cancer, including low-grade glioma (LGG) and glioblastoma (GBM), we comprehensively analyzed KIFs in 515 LGG and 595 GBM patients. Among KIFs, KIF4A, 9, 18A, and 23 showed significant clinical implications in both LGG and GBM. The mRNA and protein expression levels of KIF4A, 9, 18A, and 23 were significantly increased in LGG and GBM compared with those in the normal control groups. The mRNA expression levels of KIF4A, 9, 18A, and 23 in LGG were significantly increased in the high-histologic-grade group compared with those with a low histologic grade. Genomic analysis showed that the percent of mRNA upregulation of KIF4A, 9, 18A, and 23 was higher than that of other gene alterations, including gene amplification, deep deletion, and missense mutation. In addition, LGG patients with KIF4A, 18A, and 23 gene alterations were significantly associated with a poor prognosis. In survival analysis, the group with high expression of KIF4A, 9, 18A, and 23 mRNA was significantly associated with a poor prognosis in both LGG and GBM patients. Gene Set Enrichment Analysis (GSEA) revealed that high mRNA expression of KIF4A, 18A, and 23 in LGG and GBM patients showed significant positive correlations with the cell cycle, E2F targets, G2M checkpoint, Myc target, and mitotic spindle. By contrast, high mRNA expression of KIF9 in both LGG and GBM patients was significantly negatively correlated with the cell cycle, G2M checkpoint, and mitotic spindle pathway. However, it was significantly positively correlated with EMT and angiogenesis. This study has extended our knowledge of KIF4A, 9, 18A, and 23 in LGG and GBM and shed light on their clinical relevance, which should help to improve the treatment and prognosis of LGG and GBM.
Revealing Tumor Habitats from Texture Heterogeneity Analysis for Classification of Lung Cancer Malignancy and Aggressiveness
Authors: Cherezov Dmitry , Goldgof Dmitry , Hall Lawrence , Gillies Robert , Schabath Matthew , Müller Henning , Depeursinge Adrien 
Published: March 2019

AbstractWe propose an approach for characterizing structural heterogeneity of lung cancer nodules using Computed Tomography Texture Analysis (CTTA). Measures of heterogeneity were used to test the hypothesis that heterogeneity can be used as predictor of nodule malignancy and patient survival. To do this, we use the National Lung Screening Trial (NLST) dataset to determine if heterogeneity can represent differences between nodules in lung cancer and nodules in non-lung cancer patients. 253 participants are in the training set and 207 participants in the test set. To discriminate cancerous from non-cancerous nodules at the time of diagnosis, a combination of heterogeneity and radiomic features were evaluated to produce the best area under receiver operating characteristic curve (AUROC) of 0.85 and accuracy 81.64%. Second, we tested the hypothesis that heterogeneity can predict patient survival. We analyzed 40 patients diagnosed with lung adenocarcinoma (20 short-term and 20 long-term survival patients) using a leave-one-out cross validation approach for performance evaluation. A combination of heterogeneity features and radiomic features produce an AUROC of 0.9 and an accuracy of 85% to discriminate long- and short-term survivors.
Assessing diversity in multiplex networks
Authors: Carpi Laura C. , Schieber Tiago A. , Pardalos Panos M. , Marfany Gemma , Masoller Cristina , Díaz-Guilera Albert , Ravetti Martín G. 
Published: March 2019

AbstractDiversity, understood as the variety of different elements or configurations that an extensive system has, is a crucial property that allows maintaining the system’s functionality in a changing environment, where failures, random events or malicious attacks are often unavoidable. Despite the relevance of preserving diversity in the context of ecology, biology, transport, finances, etc., the elements or configurations that more contribute to the diversity are often unknown, and thus, they can not be protected against failures or environmental crises. This is due to the fact that there is no generic framework that allows identifying which elements or configurations have crucial roles in preserving the diversity of the system. Existing methods treat the level of heterogeneity of a system as a measure of its diversity, being unsuitable when systems are composed of a large number of elements with different attributes and types of interactions. Besides, with limited resources, one needs to find the best preservation policy, i.e., one needs to solve an optimization problem. Here we aim to bridge this gap by developing a metric between labeled graphs to compute the diversity of the system, which allows identifying the most relevant components, based on their contribution to a global diversity value. The proposed framework is suitable for large multiplex structures, which are constituted by a set of elements represented as nodes, which have different types of interactions, represented as layers. The proposed method allows us to find, in a genetic network (HIV-1), the elements with the highest diversity values, while in a European airline network, we systematically identify the companies that maximize (and those that less compromise) the variety of options for routes connecting different airports.
High-throughput screening and classification of chemicals and their effects on neuronal gene expression using RASL-seq
Authors: Simon Jeremy M. , Paranjape Smita R. , Wolter Justin M. , Salazar Gabriela , Zylka Mark J. 
Published: March 2019

AbstractWe previously used RNA-seq to identify chemicals whose effects on neuronal gene expression mimicked transcriptional signatures of autism, aging, and neurodegeneration. However, this approach was costly and time consuming, which limited our study to testing a single chemical concentration on mixed sex cortical neuron cultures. Here, we adapted a targeted transcriptomic method (RASL-seq, similar to TempO-seq) to interrogate changes in expression of a set of 56 signature genes in response to a library of 350 chemicals and chemical mixtures at four concentrations in male and female mouse neuronal cultures. This enabled us to replicate and expand our previous classifications, and show that transcriptional responses were largely equivalent between sexes. Overall, we found that RASL-seq can be used to accelerate the pace at which chemicals and mixtures that transcriptionally mimic autism and other neuropsychiatric diseases can be identified, and provides a cost-effective way to quantify gene expression with a panel of marker genes.
A new oligonucleotide array for the detection of multidrug and extensively drug-resistance tuberculosis
Authors: Chen Ching-Yu , Weng Jui-Yun , Huang Hsin-Hui , Yen Wen-Chun , Tsai Yu-Han , Cheng Tsung Chain , Jou Ruwen 
Published: March 2019

AbstractDrug-resistant tuberculosis (TB) is a global crisis and a threat to health security. Since conventional drug susceptibility testing (DST) takes several weeks, we herein described a molecular assay to rapidly identify multidrug-resistant (MDR) and extensively drug-resistant (XDR) and reveal transmission associated-mutations of Mycobacterium tuberculosis complex (MTBC) isolates in 6 to 7 hours. An array was designed with 12 pairs of primers and 60 single nucleotide polymorphisms of 9 genes: rpoB, katG, inhA, ahpC, embB, rpsL, gyrA, rrs and eis. We assessed the performance of the array using 176 clinical MTBC isolates. The results of culture-based DST were used as the gold standard, the GenoType MTBDRplus and MTBDRsl tests were used for parallel comparison, and gene sequencing was performed to resolve the discordance. The sensitivities and specificities of the array are comparable to those of the MTBDRplus test for resistance to isoniazid (INH) (100.0%, 96.7%) and rifampicin (RIF) (99.4%, 96.7%) and of the MTBDRsl test for resistance to fluoroquinolones (FQs) (100%, 100%) and second-line injectable drugs (SLIDs) (98.3%, 100%). The sensitivities of the array for detecting resistance to ethambutol and streptomycin were 79.3% and 64.9%, respectively. The array has potential as a powerful tool for clinical diagnosis and epidemiological investigations.
The effects of fatigue and oxidation on contractile function of intact muscle fibers and myofibrils isolated from the mouse diaphragm
Authors: Bagni M. Angela , Colombini Barbara , Nocella Marta , Pregno Claudio , S. Cornachione Anabelle , Rassier Dilson E. 
Published: March 2019

AbstractThe goal of this study was to investigate the effects of repetitive stimulation and the oxidant H2O2 on fatigue of diaphragm intact fibers and in myofibrils measured with different Ca2+ concentrations. Intact fibers were isolated from mice diaphragm, and twitch and tetanic contractions (500 ms duration) were performed at different frequencies of stimulation ranging from 15 Hz to 150 Hz to establish a force-frequency relation before and after a fatigue and recovery protocol, without or after a treatment with H2O2. Fatigue was induced with isometric contractions (500 ms, 40 Hz) evoked every 0.8 seconds, with a total of 625 tetani. After the fatigue, the force recovery was followed by invoking tetanic contractions (500 ms, 40 Hz) every 1 min, with a total duration of 30 min. Individual myofibrils were also isolated from the mouse diaphragm and were tested for isometric contractions before and after treatment with H2O2 and NAC. In a second series of experiments, myofibrils were activated at different pCa (pCa = −log10 [Ca2+]), before and after H2O2 treatment. After 15 minutes of H2O2 treatment, the myofibrillar force was decreased to 54 ± 12% of its control, maximal value, and a result that was reversed by NAC treatment. The force was also decreased after myofibrils were treated with H2O2 and activated in pCa ranging between 4.5 and 5.7. These results suggest that fatigue in diaphragm intact fibers and at the myofibrils level is caused partially by oxidation of the contractile proteins that may be responsible for changing the force in various levels of Ca2+ activation.
Epidermal Growth Factor Like-domain 7 and miR-126 are abnormally expressed in diffuse Systemic Sclerosis fibroblasts
Authors: Liakouli Vasiliki , Cipriani Paola , Di Benedetto Paola , Panzera Noemi , Ruscitti Piero , Pantano Ilenia , Berardicurti Onorina , Carubbi Francesco , Esteves Filomena , Mavria Georgia , Del Galdo Francesco , Giacomelli Roberto 
Published: March 2019

AbstractSystemic sclerosis (SSc) is characterized by microangiopathy with impaired reparative angiogenesis and fibrosis. Epidermal Growth Factor Like-domain 7 (EGFL7), firstly described in endothelial cells plays a pivotal role in angiogenesis. Fibroblasts (FBs) are involved in vascular remodeling, under physiological and pathological conditions. In this study, we investigated: (i) the expression of EGFL7 and its miR-126 in patients affected by diffuse cutaneous SSc (dcSSc); (ii) the ability of Transforming Growth Factor-beta (TGF-β) to modulate EGFL7 expression; (iii) the ability of EGFL7 to modulate COL1A1 expression and proliferation/migration, and (iv) the functional role of EGFL7 on angiogenesis. Patients were divided in 2 subsets: patients fulfilling the classification criteria in less than one year from Raynaud’s Phenomenon onset (Early Onset Subset–EOS), and all the others (Long Standing Subset–LSS). We show that EGFL7 expression is increased in EOS dcSSc skin and cultured FBs. EGFL7 is inducible by TGF-β on Healthy Controls (HC) FBs but not in SSc-FBs. EGFL7 decreases COL1A1 expression in EOS SSc-FBs while EGFL7 silencing up-regulates COL1A1 expression. EGFL7 promotes migration/invasion of EOS SSc-FBs but not proliferation. Finally, SSc-FBs, partially inhibit angiogenesis in organotypic coculture assays, and this is reversed by treatment with human recombinant (rh)EGFL7. We conclude that EGFL7 and its specific microRNA miR-126 may be involved in the pathogenesis of SSc vasculopathy and fibrosis.
The R229Q mutation of Rag2 does not characterize severe immunodeficiency in mice
Authors: Jin Young , Lee Ara , Oh Ja Hyun , Lee Han-Woong , Ha Sang-Jun 
Published: March 2019

AbstractRAG1 or RAG2 mutations are associated with defects in V(D)J recombination activity, causing severe immunodeficiency with a wide spectrum of clinical phenotypes. A R229Q mutation of RAG2 was identified in patients with severe combined immunodeficiency (SCID) or Omenn syndrome (OS). Although some factors determining the clinical features between SCID and OS were not clear, the molecular mechanism of OS was studied in a mouse model in which an EGFP tag is fused to Rag2 with the R229Q mutation. To design the human disease model mimicking severe immunodeficiency, we generated Rag2-R229Q knock-in mice without an epitope tag. Mutant mice showed impaired T and B cell differentiation with reduced V(D)J recombination activity; however, the extent to which the R229Q mutation affects severe immunodeficiency was not severe. While Rag2-R229Q mutation under some conditions may cause severe immunological and clinical phenotypes similar to human SCID or OS, R229Q mutation per se did not cause severe immunodeficiency in mice, suggesting that additional factors other than R229Q mutation are required to induce severe immunodeficiency. Thus, our report implies that the effects of genetic background and/or a tagged protein sequence may alter the mouse immune system, revealing the mechanism of phenotypic heterogeneity arising from an identical mutation.
Observation of a superconducting glass state in granular superconducting diamond
Authors: Klemencic G. M. , Fellows J. M. , Werrell J. M. , Mandal S. , Giblin S. R. , Smith R. A. , Williams O. A. 
Published: March 2019

AbstractThe magnetic field dependence of the superconductivity in nanocrystalline boron doped diamond thin films is reported. Evidence of a superconducting glass state is presented, as demonstrated by the observation of a quasi de Almeida-Thouless line in the phase diagram and a logarithmic time dependence of the magnetism. The position of the phase boundary in the H-T plane is determined from electrical transport data by detailed fitting to quasi-zero-dimensional fluctuation conductivity theory. This allows determination of the boundary between resistive and non-resistive behaviour to be made with greater precision than the standard ad hoc onset/midpoint/offset criterion. We attribute the glassy superconductivity to the morphological granularity of the diamond films.
CHD4 regulates the DNA damage response and RAD51 expression in glioblastoma
Authors: McKenzie Lisa D. , LeClair John W. , Miller Kayla N. , Strong Averey D. , Chan Hilda L. , Oates Edward L. , Ligon Keith L. , Brennan Cameron W. , Chheda Milan G. 
Published: March 2019

AbstractGlioblastoma (GBM) is a lethal brain tumour. Despite therapy with surgery, radiation, and alkylating chemotherapy, most people have recurrence within 6 months and die within 2 years. A major reason for recurrence is resistance to DNA damage. Here, we demonstrate that CHD4, an ATPase and member of the nucleosome remodelling and deactetylase (NuRD) complex, drives a component of this resistance. CHD4 is overexpressed in GBM specimens and cell lines. Based on The Cancer Genome Atlas and Rembrandt datasets, CHD4 expression is associated with poor prognosis in patients. While it has been known in other cancers that CHD4 goes to sites of DNA damage, we found CHD4 also regulates expression of RAD51, an essential component of the homologous recombination machinery, which repairs DNA damage. Correspondingly, CHD4 suppression results in defective DNA damage response in GBM cells. These findings demonstrate a mechanism by which CHD4 promotes GBM cell survival after DNA damaging treatments. Additionally, we found that CHD4 suppression, even in the absence of extrinsic treatment, cumulatively increases DNA damage. Lastly, we found that CHD4 is dispensable for normal human astrocyte survival. Since standard GBM treatments like radiation and temozolomide chemotherapy create DNA damage, these findings suggest an important resistance mechanism that has therapeutic implications.
Exploring designability of electrostatic complementarity at an antigen-antibody interface directed by mutagenesis, biophysical analysis, and molecular dynamics simulations
Authors: Yoshida Kouhei , Kuroda Daisuke , Kiyoshi Masato , Nakakido Makoto , Nagatoishi Satoru , Soga Shinji , Shirai Hiroki , Tsumoto Kouhei 
Published: March 2019

AbstractAntibodies protect organisms from a huge variety of foreign antigens. Antibody diversity originates from both genetic and structural levels. Antigen recognition relies on complementarity between antigen-antibody interfaces. Recent methodological advances in structural biology and the accompanying rapid increase of the number of crystal structures of proteins have enabled atomic-level manipulation of protein structures to effect alterations in function. In this study, we explored the designability of electrostatic complementarity at an antigen-antibody interface on the basis of a crystal structure of the complex. We designed several variants with altered charged residues at the interface and characterized the designed variants by surface plasmon resonance, circular dichroism, differential scanning calorimetry, and molecular dynamics simulations. Both successes and failures of the structure-based design are discussed. The variants that compensate electrostatic interactions can restore the interface complementarity, enabling the cognate antigen-antibody binding. Retrospectively, we also show that these mutational effects could be predicted by the simulations. Our study demonstrates the importance of charged residues on the physical properties of this antigen-antibody interaction and suggests that computational approaches can facilitate design of antibodies that recognize a weakly immunogenic antigen.
Dysregulation of the hypothalamic pituitary adrenal (HPA) axis and cognitive capability at older ages: individual participant meta-analysis of five cohorts
Authors: Gardner Michael , Lightman Stafford , Kuh Diana , Comijs Hannie , Deeg Dorly , Gallacher John , Geoffroy Marie-Claude , Kivimaki Mika , Kumari Meena , Power Chris , Hardy Rebecca , Richards Marcus , Ben-Shlomo Yoav 
Published: March 2019

AbstractEvidence on the association between functioning of the hypothalamic pituitary adrenal (HPA) axis and cognitive capability at older ages is mixed. We undertook a systematic review (until October 2016) and individual participant data (IPD) meta-analysis to test if dysregulation of the HPA axis is associated with worse cognitive capability. Five cohort studies were included in the IPD meta-analysis of diurnal cortisol patterns with crystallised and fluid cognitive ability. Higher night time cortisol was associated with worse fluid ability (standardised coefficient per SD increase −0.063, 95% CI −0.124, −0.002,P = 0.04; I2 = 79.9%; age and gender adjusted). A larger diurnal drop was associated with better fluid ability (standardised coefficient per SD increase 0.037, 95% CI 0.008, 0.065,P = 0.01; I2 = 49.2%; age and gender adjusted). A bigger cortisol awakening response (CAR) was weakly associated with better fluid (P = 0.09; I2 = 0.0%; age and gender adjusted) and crystallised (P = 0.10; I2 = 0.0%; age and gender adjusted) ability. There is weak evidence that a greater diurnal decline of the HPA axis and a larger CAR are associated with improvements in cognition at older ages. As associations are cross-sectional, we cannot rule out reverse causation.
Immutable heavy metal pollution before and after change in industrial waste treatment procedure
Authors: Ozaki Hirokazu , Ichise Hiroshi , Kitaura Emi , Yaginuma Yuki , Yoda Masaaki , Kuno Katsuji , Watanabe Izumi 
Published: March 2019

AbstractThis study compared state of pollution around an intermediate treatment plant of industrial wastes before and after the change of its treatment procedure. Bulk atmospheric deposition, surface soil, suspended particulate matter and groundwater were collected after the plant changed main operation to waste crushing and volume reduction. Their heavy metals content were comparatively investigated with the previous results obtained when it was burning wastes. The bulk heavy metals deposition showed a clear distance-related attenuation both in burning and crushing periods, indicating that the plant was the main emissions source in either case. High concentrations of heavy metals in suspended particles, soil, and groundwater during the crushing period indicated their diffusion to water environment over time. The bulk atmospheric heavy metals deposition decreased significantly, 0.20~ 0.49 times for Cu, Zn, Cd and Pb and 0.69~0.94 times for Cr, during the crushing period than burning period. However, change of their enrichment factors was not significant. It may indicate that the pollution state did not change qualitatively in a bulk deposition basis and quantitatively in a depositing particle basis. The results showed that heavy metals deposition is dominated by suspended and precipitated particulate matters that adsorb and transport the metals.