bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disrupted glycosylation of lipids and proteins is a cause of neurodegeneration
Authors: Moll Tobias , Shaw Pamela J , Cooper-Knock Johnathan 
Published: October 2019

AbstractGlycosyltransferases represent a large family of enzymes that catalyse the biosynthesis of oligosaccharides, polysaccharides, and glycoconjugates. A number of studies have implicated glycosyltransferases in the pathogenesis of neurodegenerative diseases but differentiating cause from effect has been difficult. We have recently discovered that mutations proximal to the substrate binding site of glycosyltransferase 8 domain containing 1 (GLT8D1) are associated with familial amyotrophic lateral sclerosis (ALS). We demonstrated that ALS-associated mutations reduce activity of the enzyme suggesting a loss-of-function mechanism that is an attractive therapeutic target. Our work is the first evidence that isolated dysfunction of a glycosyltransferase is sufficient to cause a neurodegenerative disease, but connection between neurodegeneration and genetic variation within glycosyltransferases is not new. Previous studies have identified associations between mutations in UGT8 and sporadic ALS, and between ST6GAL1 mutations and conversion of mild cognitive impairment into clinical Alzheimer’s disease. In this review we consider potential mechanisms connecting glycosyltransferase dysfunction to neurodegeneration. The most prominent candidates are ganglioside synthesis and impaired addition of O-linked β-N-acetylglucosamine (O-GlcNAc) groups to proteins important for axonal and synaptic function. Special consideration is given to examples where genetic mutations within glycosyltransferases are associated with neurodegeneration in recognition of the fact that these changes are likely to be upstream causes present from birth.
Loss of ARID1A induces a stemness gene ALDH1A1 expression with histone acetylation in the malignant subtype of cholangiocarcinoma
Authors: Yoshino Jun , Akiyama Yoshimitsu , Shimada Shu , Ogura Toshiro , Ogawa Kosuke , Ono Hiroaki , Mitsunori Yusuke , Ban Daisuke , Kudo Atsushi , Yamaoka Shoji , Tanabe Minoru , Tanaka Shinji 
Published: October 2019

Abstract
Genomic analyses have recently discovered the malignant subtype of human intrahepatic cholangiocarcinoma (ICC) characterized by frequent mutations of chromatin remodeling gene ARID1A; however, the biological and molecular functions still remain obscure. We here examined the clinical and biological significances of ARID1A deficiency in human ICC. Immunohistochemical analysis demonstrated that the loss of ARID1A was an independent prognostic factor for overall survival of ICC patients (P = 0.023). We established ARID1A-knockout (KO) cells by using the CRISPR/Cas9 system from two human cholangiocarcinoma cell lines. ARID1A-KO cells exhibited significantly enhanced migration, invasion, and sphere formation activity. Microarray analysis revealed that ALDH1A1, a stemness gene, was the most significantly elevated genes in ARID1A-KO cells. In addition, ALDH enzymatic activity as a hallmark of cancer stem cells was markedly high in the KO cells. ARID1A and histone deacetylase 1 were directly recruited to the ALDH1A1 promoter region in cholangiocarcinoma cells with undetectable ALDH1A1 expression by chromatin immunoprecipitation assay. The histone H3K27 acetylation level at the ALDH1A1 promoter region was increased in cells when ARID1A was disrupted (P &lt; 0.01). Clinically, inverse correlation between ARID1A and ALDH1A1 expression was also identified in primary ICC (P = 0.018), and ARID1A-negative and ALDH1A1-positve ICCs showed worse prognosis than only ARID1A-negative cases (P = 0.002). In conclusion, ARID1A may function as a tumor suppressor in ICC through transcriptional downregulation of ALDH1A1 expression with decreasing histone H3K27 acetylation. Our studies provide the basis for the development of new epigenetic approaches to ARID1A-negative ICC.
Immunohistochemical loss of ARID1A is an independent prognostic factor in intrahepatic cholangiocarcinoma patients. ARID1A recruits HDAC1 to the promoter region of ALDH1A1, a stemness gene, and epigenetically suppresses ALDH1A1 expression with decreasing histone H3K27 acetylation in cholangiocarcinoma cells.
Cefazolin and Ertapenem Salvage Therapy Rapidly Clears Persistent Methicillin-Susceptible Staphylococcus aureus Bacteremia
Authors: Ulloa Erlinda R , Singh Kavindra V , Geriak Matthew , Haddad Fadi , Murray Barbara E , Nizet Victor , Sakoulas George 
Published: October 2019

Abstract
Cefazolin and ertapenem combination therapy was used successfully to salvage 11 cases (6 endocarditis) of persistent methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, including immediate clearance (≤24 hours) in 8 cases. While in vitro synergy was modest, cefazolin plus ertapenem exhibited synergistic action in a rat model of MSSA endocarditis. The combination of cefazolin and ertapenem provides potent in vivo activity against MSSA beyond what is predicted in vitro and warrants further clinical study in the treatment of refractory MSSA bacteremia and endocarditis.
‘But the Last Word Is Ours’: The Monopoly of Jurisdiction of the Court of Justice of the European Union in Light of the Investment Court System
Authors: de Abreu Duarte Francisco 
Published: October 2019

Abstract
This article develops the concept of the monopoly of jurisdiction of the Court of Justice of the European Union (CJEU) through the analysis of the case study of the Investment Court System (ICS). By providing a general framework over the criteria that have been developed by the Court, the work sheds light on the controversial principle of autonomy of the European Union (EU) and its implications to the EU’s external action. The work intends to be both pragmatic and analytical. On the one hand, the criteria are extracted as operative tools from the jurisprudence of the CJEU and then used in the context of the validity of the ICS. This provides the reader with some definitive standards that can then be applied to future cases whenever a question concerning autonomy arises. On the other hand, the article questions the reasons behind the idea of the monopoly of jurisdiction of the CJEU, advancing a concept of autonomy of the EU as a claim for power and critiquing the legitimacy and coherence of its foundations. Both dimensions will hopefully help to provide some clarity over the meaning of autonomy and the monopoly of jurisdiction, while, at the same time, promoting a larger discussion on its impact on the external action of the EU.
A comparison of prokaryote communities inhabiting sponges, bacterial mats, sediment and seawater in Southeast Asian coral reefs
Authors: Cleary DFR , Polónia ARM , Huang YM , Putchakarn S , Gomes NCM , de Voogd NJ 
Published: October 2019

Abstract
In the present study, we used Illumina sequencing to explore the prokaryote communities of 17 demosponge species and how they compare with bacterial mat, sediment and seawater samples (all sampled from coral reef habitat in Taiwan and Thailand). The studied sponge species formed three clusters. OTU richness and evenness were by far highest in the sediment and bacterial mat biotopes. There were pronounced differences in OTU richness and evenness among clusters and also considerable variation among certain host species within clusters. Additionally, the relative abundance of some prokaryotic taxa also differed among clusters with Poribacteria, for example, being recorded in all sponge species, but with very low relative abundances in species of two of the three clusters. This sponge-associated phylum was, however, recorded at relatively high mean abundance in bacterial mat samples, which also housed relatively high abundances of actinobacterial and Chloroflexi members. Our results support the HMA status of the species Aaptos lobata, Hyrtios erectus, Pseudoceratina purpurea and Xestospongia testudinaria, which clustered together and LMA status of the species Acanthella cavernosa, Echinodictyum asperum, Jaspis splendens, Ptilocaulis spiculifer, Stylissa carteri and Suberites diversicolor, which also clustered together. Other species (Agelas cavernosa, Agelas nemoechinata, Acanthostylotella cornuta, Paratetilla sp., Hymeniacidon sp. and Haliclona cymaeformis) deviated somewhat from the typical HMA/LMA dichotomy and formed a strongly supported cluster.
GingerRoot: A Novel DNA Transposon Encoding Integrase-Related Transposase in Plants and Animals
Authors: Cerbin Stefan , Wai Ching Man , VanBuren Robert , Jiang Ning 
Published: October 2019

AbstractTransposable elements represent the largest components of many eukaryotic genomes and different genomes harbor different combinations of elements. Here, we discovered a novel DNA transposon in the genome of the clubmoss Selaginella lepidophylla. Further searching for related sequences to the conserved DDE region uncovered the presence of this superfamily of elements in fish, coral, sea anemone, and other animal species. However, this element appears restricted to Bryophytes and Lycophytes in plants. This transposon, named GingerRoot, is associated with a 6 bp (base pair) target site duplication, and 100–150 bp terminal inverted repeats. Analysis of transposase sequences identified the DDE motif, a catalytic domain, which shows similarity to the integrase of Gypsy-like long terminal repeat retrotransposons, the most abundant component in plant genomes. A total of 77 intact and several hundred truncated copies of GingerRoot elements were identified in S. lepidophylla. Like Gypsy retrotransposons, GingerRoots show a lack of insertion preference near genes, which contrasts to the compact genome size of about 100 Mb. Nevertheless, a considerable portion of GingerRoot elements was found to carry gene fragments, suggesting the capacity of duplicating gene sequences is unlikely attributed to the proximity to genes. Elements carrying gene fragments appear to be less methylated, more diverged, and more distal to genes than those without gene fragments, indicating they are preferentially retained in gene-poor regions. This study has identified a broadly dispersed, novel DNA transposon, and the first plant DNA transposon with an integrase-related transposase, suggesting the possibility of de novo formation of Gypsy-like elements in plants.
DNA methylation age and physical and cognitive ageing
Authors: Maddock Jane , Castillo-Fernandez Juan , Wong Andrew , Cooper Rachel , Richards Marcus , Ong Ken K , Ploubidis George B , Goodman Alissa , Kuh Diana , Bell Jordana T , Hardy Rebecca 
Published: October 2019

Abstract

Background
DNA methylation (DNAm) age acceleration (AgeAccel) has been shown to be predictive of all-cause mortality but it is unclear what functional aspect/s of ageing it captures. We examine associations between four measures of AgeAccel in adults aged 45-87 years and physical and cognitive performance and their age-related decline.

Methods
AgeAccelHannum, AgeAccelHorvath, AgeAccelPheno and AgeAccelGrim were calculated in the Medical Research Council National Survey of Health and Development (NSHD), National Child Development Study (NCDS) and TwinsUK. Three measures of physical (grip strength, chair rise speed and forced expiratory volume in one second[FEV1]) and two measures of cognitive (episodic memory and mental speed) performance were assessed.

Results
AgeAccelPheno and AgeAccelGrim, but not AgeAccelHannum and AgeAccelHorvath were related to performance in random effects meta-analyses (n=1388-1685). For example, a one year increase in AgeAccelPheno/AgeAccelGrim was associated with a 0.01ml[95%CI:0.01,0.02]/0.03ml[95%CI:0.01,0.05] lower mean FEV1. In NSHD, AgeAccelPheno and AgeAccelGrim at 53 years were associated with age-related decline in performance between 53 and 69 years as tested by linear mixed models (p<0.05). In a subset of NSHD participants(n=482), there was little evidence that change in any AgeAccel measure was associated with change in performance conditional on baseline performance.

Conclusions
We found little evidence to support associations between the first generation of DNAm-based biomarkers of ageing and age-related physical or cognitive performance in mid-life to early old age. However, there was evidence that the second generation biomarkers, AgeAccelPheno and AgeAccelGrim, could act as makers of an individual’s health-span as proposed.
Rare palaeomagnetic evidence of long-term mantle control of the geodynamo and possible role of the NAD field in the reversal process
Authors: Hoffman Kenneth A , Camps Pierre , Carlton Matt 
Published: October 2019

SUMMARY
The degree to which the lowermost mantle influences behaviour of the geodynamo has been debated over the past quarter century. Our analysis of a comprehensive set of 17 Cenozoic palaeomagnetic transitional field records obtained from lavas in the Southern Hemisphere provides robust evidence of stable mantle control since the Pliocene. The records come from a region where—given a significantly weakened axial dipole—the magnetic field today would be largely controlled by the non-axial dipole (NAD) flux patch currently emanating from Earth's outer core beneath western Australia. The palaeomagnetic recording sites from west to east include the south Indian Ocean, eastern Australia, New Zealand and French Polynesia. The analysed records contain from 2 to 26 sequential transitional virtual geomagnetic poles (VGPs). 10 of the 17 records supply at least one VGP within a narrow longitudinal band 10°-wide between 60°S and the equator, centred along 102.4°E. That is, transitional data from 59 per cent of the Cenozoic recordings are found to reside in a region that encompasses a mere 2.8 per cent of the VGP transitional area on Earth's surface. A robust Monte Carlo approach applied to this data set, one that takes into account the number of transitional VGPs contained in each record, finds this result highly improbable (p-value = 0.0006). The present-day pattern of vertical flux at the core–mantle boundary shows an anomalously strong, thin Southern Hemisphere longitudinal band off the west coast of Australia that strikingly coincides with this unusual palaeomagnetic finding. We conclude with a high degree of confidence that this band of flux has remained virtually unmoved for at least the past 3 Myr. Seemingly independent of the behaviour of the axial dipole, our findings indicate that it has dominated the magnetic field over an area of considerable size during attempts by the geodynamo to reverse polarity.
Sources of uncertainties and artifacts in back-projection results
Authors: Hongyu Zeng , Shengji Wei , Wenbo Wu 
Published: October 2019

Summary
Back-projecting high-frequency (HF) waves is a common procedure for imaging rupture processes of large earthquakes (i.e. Mw > 7.0). However, obtained back-projection (BP) results could suffer from large uncertainties since high-frequency seismic waveforms are strongly affected by factors like source depth, focal mechanisms, and the Earth's 3D velocity structures. So far, these uncertainties have not been thoroughly investigated. Here, we use synthetic tests to investigate the influencing factors for which scenarios with various source and/or velocity set-ups are designed, using either Tohoku-Oki (Japan), Kaikoura (New Zealand), Java/Wharton Basin (Indonesia) as test areas. For the scenarios, we generate either 1D or 3D teleseismic synthetic data, which are then back-projected using a representative BP method, MUltiple SIgnal Classification (MUSIC). We also analyze corresponding real cases to verify the synthetic test results. The Tohoku-Oki scenario shows that depth phases of a point source can be back-projected as artifacts at their bounce points on the earth's surface, with these artifacts located far away from the epicenter if earthquakes occur at large depths, which could significantly contaminate BP images of large intermediate-depth earthquakes. The Kaikoura scenario shows that for complicated earthquakes, composed of multiple sub-events with varying focal mechanisms, BP tends to image sub-events emanating large amplitude coherent waveforms, while missing sub-events whose P nodal directions point to the arrays, leading to discrepancies either between BP images from different arrays, or between BP images and other source models. Using the Java event, we investigate the impact of 3D source-side velocity structures. The 3D bathymetry together with a water layer can generate strong and long-lasting coda waves, which are mirrored as artifacts far from the true source location. Finally, we use a Wharton Basin outer-rise event to show that the wavefields generated by 3D near trench structures contain frequency-dependent coda waves, leading to frequency-dependent BP results. In summary, our analyses indicate that depth phases, focal mechanism variations, and 3D source-side structures can affect various aspects of BP results. Thus, we suggest that target-oriented synthetic tests, for example, synthetic tests for subduction earthquakes using more realistic 3D source-side velocity structures, should be conducted to understand the uncertainties and artifacts before we interpret detailed BP images to infer earthquake rupture kinematics and dynamics.
Genome-wide heritability analysis of severe malaria resistance reveals evidence of polygenic inheritance
Authors: Damena Delesa , Chimusa Emile R 
Published: October 2019

Abstract
Background: Estimating single nucleotide polymorphism (SNP)-heritability (h2g) of severe malaria resistance and its distribution across the genome might shed new light in to the underlying biology. Method: We investigated h2g of severe malaria resistance from a genome-wide association study (GWAS) dataset (sample size = 11 657). We estimated the h2g and partitioned in to chromosomes, allele frequencies and annotations using the genetic relationship-matrix restricted maximum likelihood approach. We further examined non-cell type-specific and cell type-specific enrichments from GWAS-summary statistics. Results: The h2g of severe malaria resistance was estimated at 0.21 (se = 0.05, P = 2.7 × 10−5), 0.20 (se = 0.05, P = 7.5 × 10−5) and 0.17 (se = 0.05, P = 7.2 × 10−4) in Gambian, Kenyan and Malawi populations, respectively. A comparable range of h2g [0.21 (se = 0.02, P &lt; 1 × 10−5)] was estimated from GWAS-summary statistics meta-analysed across the three populations. Partitioning analysis from raw genotype data showed significant enrichment of h2g in genic SNPs while summary statistics analysis suggests evidences of enrichment in multiple categories. Supporting the polygenic inheritance, the h2g of severe malaria resistance is distributed across the chromosomes and allelic frequency spectrum. However, the h2g is disproportionately concentrated on three chromosomes (chr 5, 11 and 20), suggesting cost-effectiveness of targeting these chromosomes in future malaria genomic sequencing studies. Conclusion: We report for the first time that the heritability of malaria resistance is largely ascribed by common SNPs and the causal variants are overrepresented in protein coding regions of the genome. Further studies with larger sample sizes are needed to better understand the underpinning genetics of severe malaria resistance.
Rational or Irrational Decision? Examination on Gamers’ Intention to Purchase Probability-Type Items
Authors: Seo Young-nam , Jung Younbo , Sng Jeremy , Park Jongmin 
Published: October 2019

Abstract
Expanding the theory of planned behavior (TPB) model with non-volitional factors, this study investigated determinants of purchase intention (PI) for probability-type items (PTI) in a popular mobile game. An online survey was conducted with 534 players of Summoners War. The overall results show that the PI of PTI is associated with both rational and impulsive factors. Specifically, the results of hierarchical regression analysis demonstrate that along with two TPB elements (attitude and perceived control), individual factors of self-control and general stress, as well as game-related factors of advancement, competition, purchase frequency and spending amount were all significant predictors of PTI PI. These non-volitional factors account for additional 18% of variance out of 48% total variance (R2 = .48) in PI.
Tandem amplification of the vanM gene cluster drives vancomycin resistance in vancomycin-variable enterococci
Authors: Sun Lingyan , Chen Yan , Hua Xiaoting , Chen Yiyi , Hong Jinjing , Wu Xueqing , Jiang Yan , van Schaik Willem , Qu Tingting , Yu Yunsong 
Published: October 2019

AbstractBackgroundVancomycin-variable enterococci (VVE) are a potential risk factor for vancomycin resistance gene dissemination and clinical treatment failure. vanM has emerged as a new prevalent resistance determinant among clinical enterococci in China. A total of 54 vancomycin-susceptible enterococci (VSE) isolates carrying incomplete vanM gene clusters were isolated in our previous study.ObjectivesTo determine the potential of vanM-carrying VSE to develop vancomycin resistance and investigate the mechanism of alteration of the resistance phenotype.MethodsFifty-four vanM-positive VSE strains were induced in vitro by culturing in increasing concentrations of vancomycin. Genetic changes between three parent VVE strains and their resistant variants were analysed using Illumina and long-read sequencing technologies, quantitative PCR and Southern blot hybridization. Changes in expression level were determined by quantitative RT–PCR.ResultsTwenty-five of the 54 VSE strains carrying vanM became resistant upon vancomycin exposure. A significant increase in vanM copy number was observed ranging from 5.28 to 127.64 copies per cell in induced resistant VVE strains. The vanM transposon was identified as tandem repeats with IS1216E between them, and occurred in either the plasmid or the chromosome of resistant VVE cells. In addition, an increase in vanM expression was observed after resistance conversion in VVE.ConclusionsThis study identified tandem amplification of the vanM gene cluster as a new mechanism for vancomycin resistance in VVE strains, offering a competitive advantage for VVE under antibiotic pressure.
Regrafting of the Split-Thickness Skin Graft Donor-Site: Is It Beneficial?
Authors: Legemate Catherine M , Lucas Ymke , Oen Irma M M H , Van Der Vlies Cornelis H 
Published: October 2019

Abstract
Split-thickness skin grafting remains a fundamental treatment for patients with deep burns and other traumatic injuries. Unfortunately, the donor site wound that remains after split skin graft (SSG) harvesting may also cause problems for the patient; they can lead to discomfort and scars with a poor cosmetic outcome. Regrafting of the donor site is one of the methods described to improve donor site healing and scarring. In this report, we describe a case of a 26-year-old woman with a self-inflicted chemical burn (0.5% TBSA) who underwent split skin grafting. During surgery, only part of the donor site was regrafted with split skin graft remnants. This part healed faster and had a better scar quality at 3 months postsurgery. Nevertheless, the appearance and patients’ opinion on the regrafted part deteriorated after 12 months. With this case report, we aim to create awareness of the long-term consequences of regrafting, which may differ from short-time results. Patients expected to have poor reepithelialization potential may benefit from regrafting of the SSG on the donor site. But in healthy young individuals, timewise there would be no benefit since it can lead to an aesthetically displeasing result.