bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of fluoroquinolones in dusts from intensive livestock farming and the co-occurrence of fluoroquinolone-resistant Escherichia coli
Authors: Schulz Jochen , Kemper Nicole , Hartung Joerg , Janusch Franziska , Mohring Siegrun A. I. , Hamscher Gerd 
Published: March 2019

AbstractFluoroquinolones are important therapeutics in human and veterinary medicine. This study aimed to retrospectively analyse sedimentation dusts from intensive-livestock-farming barns for fluoroquinolones and investigate the association between resistant Escherichia coli and the detected drugs. Sedimentation-dust samples (n = 125) collected (1980–2009) at 14 barns of unknown-treatment status were analysed by HPLC and tandem-mass spectroscopy to detect enrofloxacin, ciprofloxacin, marbofloxacin, and difloxacin. Recent microbiological data were included to investigate the relationship between fluoroquinolone presence and fluoroquinolone-resistant E. coli. Fifty-nine dust samples (47%) from seven barns contained fluoroquinolone residues. Up to three different fluoroquinolones were detected in pig and broiler barns. Fluoroquinolone concentrations ranged from 10-pg/mg to 46-ng/mg dust. Fluoroquinolone-resistant E. coli were isolated from four barns. Of all the dust samples, 22% contained non-susceptible isolates. Non-susceptible isolate presence in the dust was significantly associated (p = 0.0283) with detecting the drugs, while drug detection increased the odds (4-fold) of finding non-susceptible E. coli (odds ratio = 3.9877, 95% CI: 1.2854–12.3712). This retrospective study shows that fluoroquinolone usage leads to dust contamination. We conclude that farmers and animals inhale/swallow fluoroquinolones and fluoroquinolone-resistant bacteria due to drug application. Furthermore, uncontrolled drug emissions via air exhausted from the barns can be assumed.
A multi-stage association study of plasma cytokines identifies osteopontin as a biomarker for acute coronary syndrome risk and severity
Authors: Yu Kuai , Yang Binyao , Jiang Haijing , Li Jun , Yan Kai , Liu Xuezhen , Zhou Lue , Yang Handong , Li Xiulou , Min Xinwen , Zhang Ce , Luo Xiaoting , Mei Wenhua , Sun Shunchang , Zhang Liyun , Cheng Xiang , He Meian , Zhang Xiaomin , Pan An , Hu Frank B. , Wu Tangchun 
Published: March 2019

AbstractCytokines play a critical role in the pathogenesis and development of cardiovascular diseases. However, data linking cytokines to risk and severity of acute coronary syndrome (ACS) are still limited. We measured plasma profile of 280 cytokines using a quantitative protein microarray in 12 ACS patients and 16 healthy controls, and identified 15 differentially expressed cytokines for ACS. Osteopontin, chemokine ligand 23, brain derived neurotrophic factor and C-reactive protein (CRP) were further validated using immunoassay in two independent case-control studies with a total of 210 ACS patients and 210 controls. We further examined their relations with incident ACS among 318 case-control pairs nested within the Dongfeng-Tongji cohort, and found plasma osteopontin and CRP concentrations were associated with incident ACS, and the multivariable-adjusted odds ratio (95% confidence interval) was 1.29 (1.06–1.57) per 1-SD increase for osteopontin and 1.30 (1.02–1.66) for CRP, respectively. Higher levels of circulating osteopontin were also correlated with higher severity of ACS, and earlier ACS onset time. Adding osteopontin alone or in combination with CRP modestly improved the predictive ability of ACS beyond the Framingham risk scores. Our findings suggested that osteopontin might be a biomarker for incident ACS, using osteopontin adds moderately to traditional cardiovascular risk factors.
Relationship of the orange tissue morphotype with shell and pearl colouration in the mollusc Pinctada margaritifera
Authors: Ky Chin-Long , Blay Carole , Broustal Floriane , Sham Koua Manaarii , Planes Serge 
Published: March 2019

AbstractMolluscs display a vast range of shell colours both between and within species. However, only a few species show colour variation in their soft tissues. In French Polynesia, the pearl oyster Pinctada margaritifera has three tissue morphotypes: the black wild-type and two rare mutations: white albino and orange mantle. Phenotypic transmission is known to occur from these phenotypes when they are used as graft donors for pearl production, leading to multicoloured and white pearls from black and albino mantle grafts, respectively. The present study furthers this knowledge by examining the phenotypic association between the orange mantle tissue morphotype and hard tissues: shells and cultured pearls. Based on a large experimental graft, shell colour quantification and pearl qualification showed that the orange morphotype is associated with light-coloured shells and pearls. Expression analysis of some candidate genes previously identified in the white mantle mutant, tested here on both graft and pearl sac tissues from orange mantle donors, confirmed the involvement of genes associated with shell matrix protein (shem4) and the melanin biosynthesis pathway (zinc). This study provides fundamental information on the mechanism behind mantle tissue colour in P. margaritifera and its association with biomineralisation and pigmentation processes that will be potentially valuable in future selection programs.
A combined gene expression tool for parallel histological prediction and gene fusion detection in non-small cell lung cancer
Authors: Karlsson Anna , Cirenajwis Helena , Ericson-Lindquist Kajsa , Brunnström Hans , Reuterswärd Christel , Jönsson Mats , Ortiz-Villalón Cristian , Hussein Aziz , Bergman Bengt , Vikström Anders , Monsef Nastaran , Branden Eva , Koyi Hirsh , de Petris Luigi , Micke Patrick , Patthey Annika , Behndig Annelie F. , Johansson Mikael , Planck Maria , Staaf Johan 
Published: March 2019

AbstractAccurate histological classification and identification of fusion genes represent two cornerstones of clinical diagnostics in non-small cell lung cancer (NSCLC). Here, we present a NanoString gene expression platform and a novel platform-independent, single sample predictor (SSP) of NSCLC histology for combined, simultaneous, histological classification and fusion gene detection in minimal formalin fixed paraffin embedded (FFPE) tissue. The SSP was developed in 68 NSCLC tumors of adenocarcinoma (AC), squamous cell carcinoma (SqCC) and large-cell neuroendocrine carcinoma (LCNEC) histology, based on NanoString expression of 11 (CHGA, SYP, CD56, SFTPG, NAPSA, TTF-1, TP73L, KRT6A, KRT5, KRT40, KRT16) relevant genes for IHC-based NSCLC histology classification. The SSP was combined with a gene fusion detection module (analyzing ALK, RET, ROS1, MET, NRG1, and NTRK1) into a multicomponent NanoString assay. The histological SSP was validated in six cohorts varying in size (n = 11–199), tissue origin (early or advanced disease), histological composition (including undifferentiated cancer), and gene expression platform. Fusion gene detection revealed five EML4-ALK fusions, four KIF5B-RET fusions, two CD74-NRG1 fusion and three MET exon 14 skipping events among 131 tested cases. The histological SSP was successfully trained and tested in the development cohort (mean AUC = 0.96 in iterated test sets). The SSP proved successful in predicting histology of NSCLC tumors of well-defined subgroups and difficult undifferentiated morphology irrespective of gene expression data platform. Discrepancies between gene expression prediction and histologic diagnosis included cases with mixed histologies, true large cell carcinomas, or poorly differentiated adenocarcinomas with mucin expression. In summary, we present a proof-of-concept multicomponent assay for parallel histological classification and multiplexed fusion gene detection in archival tissue, including a novel platform-independent histological SSP classifier. The assay and SSP could serve as a promising complement in the routine evaluation of diagnostic lung cancer biopsies.
Mutational and non mutational adaptation of Salmonella enterica to the gall bladder
Authors: Urdaneta Verónica , Hernández Sara B. , Casadesús Josep 
Published: March 2019

AbstractDuring systemic infection of susceptible hosts, Salmonella enterica colonizes the gall bladder, which contains lethal concentrations of bile salts. Recovery of Salmonella cells from the gall bladder of infected mice yields two types of isolates: (i) bile-resistant mutants; (ii) isolates that survive lethal selection without mutation. Bile-resistant mutants are recovered at frequencies high enough to suggest that increased mutation rates may occur in the gall bladder, thus providing a tentative example of stress-induced mutation in a natural environment. However, most bile-resistant mutants characterized in this study show defects in traits that are relevant for Salmonella colonization of the animal host. Mutation may thus permit short-term adaptation to the gall bladder at the expense of losing fitness for transmission to new hosts. In contrast, non mutational adaptation may have evolved as a fitness-preserving strategy. Failure of RpoS− mutants to colonize the gall bladder supports the involvement of the general stress response in non mutational adaptation.
CCL21/CCR7 axis regulating juvenile cartilage repair can enhance cartilage healing in adults
Authors: Joutoku Zenta , Onodera Tomohiro , Matsuoka Masatake , Homan Kentaro , Momma Daisuke , Baba Rikiya , Hontani Kazutoshi , Hamasaki Masanari , Matsubara Shinji , Hishimura Ryosuke , Iwasaki Norimasa 
Published: March 2019

AbstractJuvenile tissue healing is capable of extensive scarless healing that is distinct from the scar-forming process of the adult healing response. Although many growth factors can be found in the juvenile healing process, the molecular mechanisms of juvenile tissue healing are poorly understood. Here we show that juvenile mice deficient in the chemokine receptor CCR7 exhibit diminished large-scale healing potential, whereas CCR7-depleted adult mice undergo normal scar-forming healing similar to wild type mice. In addition, the CCR7 ligand CCL21 was transiently expressed around damaged cartilage in juvenile mice, whereas it is rarely expressed in adults. Notably, exogenous CCL21 administration to adults decreased scar-forming healing and enhanced hyaline-cartilage repair in rabbit osteochondral defects. Our data indicate that the CCL21/CCR7 axis may play a role in the molecular control mechanism of juvenile cartilage repair, raising the possibility that agents modulating the production of CCL21in vivocan improve the quality of cartilage repair in adults. Such a strategy may prevent post-traumatic arthritis by mimicking the self-repair in juvenile individuals.
Upregulation of NDRG1 predicts poor outcome and facilitates disease progression by influencing the EMT process in bladder cancer
Authors: Li Aiwei , Zhu Xi , Wang Chanjuan , Yang Shuo , Qiao Yan , Qiao Rui , Zhang Jie 
Published: March 2019

AbstractN-myc downstream regulated gene 1 (NDRG1) is an intracellular protein involved in cell differentiation and was recently reported to exert various effects in several cancers. However, its expression and role in bladder cancer remain unclear. Our study enrolled 100 bladder cancer patients to detect NDRG1 expression in tumour tissues by immunohistochemistry. Correlations between NDRG1 expression and clinical factors were analysed. An NDRG1 overexpression plasmid and NDRG1 siRNAs were transfected into bladder cancer cell lines. Cell biological behaviours were assessed by CCK-8, flow cytometry, wound healing and Transwell assays. Additionally, the influence of NDRG1 on epithelial-mesenchymal transition (EMT) was investigated by western blotting and real-time PCR. NDRG1 expression in urine from bladder cancer patients was examined by ELISA. NDRG1 protein levels were significantly increased in bladder cancer patients and correlated with tumour stage (p = 0.025), lymph node metastasis (p = 0.034) and overall survival (p = 0.016). Patients with high NDRG1 expression had poorer outcomes than those with low NDRG1 expression. NDRG1 overexpression was associated with increased cell proliferation, migration, and invasion and decreased apoptotic cell numbers; NDRG1 knockdown resulted in the inverse effects. Moreover, upregulated NDRG1 expression was associated with downregulated Cytokeratin 7 and Claudin-1 expression and upregulated N-cad, β-catenin and slug expression. Downregulated NDRG1 expression was associated with the inverse effects. Urine protein levels could distinguish bladder cancer patients from healthy controls, with an area under the curve of 0.909. NDRG1 promoted EMT in bladder cancer and could be an effective diagnostic and prognostic biomarker in bladder cancer patients.
Utilization of NGS technologies to investigate transcriptomic and epigenomic mechanisms in trastuzumab resistance
Authors: Nava Miguel , Dutta Pranabananda , Farias-Eisner Robin , Vadgama Jaydutt V. , Wu Yanyuan 
Published: March 2019

AbstractNGS (Next Generation Sequencing) technologies allows us to determine key gene expression signatures that correlate with resistance (and responsiveness) to anti-cancer therapeutics. We have undertaken a transcriptomic and chromatin immunoprecipitation followed by sequencing (ChIP-seq) approach to describe differences in gene expression and the underlying chromatin landscape between two representative HER2+ cell lines, one of which is sensitive (SKBR3) and the other which is resistant (JIMT1) to trastuzumab. We identified differentially expressed genes (DEGs) and differentially expressed transcripts (DETs) between SKBR3 and JIMT1 cells. Several of the DEGs are components of the Polycomb Repressing Complex 2 (PRC2), and they are expressed higher in JIMT1 cells. In addition, we utilized ChIP-seq to identify H3K18ac, H3K27ac and H3K27me3 histone modifications genome-wide. We identified key differences of H3K18ac and H3K27ac enrichment in regulatory regions, found a correlation between these modifications and differential gene expression and identified a transcription factor binding motif for LRF near these modifications in both cell lines. Lastly, we found a small subset of genes that contain repressive H3K27me3 marks near the gene body in SKBR3 cells but are absent in JIMT1. Taken together, our data suggests that differential gene expression and trastuzumab responsiveness in JIMT1 and SKBR3 is determined by epigenetic mechanisms.
Cognitive correlates of abnormal myelination in psychosis
Authors: Vanes Lucy D. , Mouchlianitis Elias , Barry Erica , Patel Krisna , Wong Katie , Shergill Sukhwinder S. 
Published: March 2019

AbstractPsychotic illness has consistently been associated with deficits in cognitive function and reduced white matter integrity in the brain. However, the link between white matter disruptions and deficits in cognitive domains remains poorly understood. We assessed cognitive performance and white matter myelin water fraction (MWF) using multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) in recent-onset psychosis patients and age-matched healthy controls (HC). Psychosis patients showed deficits in working memory, phonological and semantic fluency, general intelligence quotient and reduced MWF in the left temporal white matter compared to HC. MWF in the left inferior fronto-occipital fasciculus and inferior longitudinal fasciculus was positively associated with intelligence quotient and verbal fluency in patients, and fully mediated group differences in performance in both phonological and semantic verbal fluency. There was no association between working memory and MWF in the left temporal white matter. Negative symptoms demonstrated a negative association with MWF within the left inferior and superior longitudinal fasciculi. These findings indicate that psychosis-related deficits in distinct cognitive domains, such as verbal fluency and working memory, are not underpinned by a single common dysfunction in white matter connectivity.
Novel diversity within marine Mamiellophyceae (Chlorophyta) unveiled by metabarcoding
Authors: Tragin Margot , Vaulot Daniel 
Published: March 2019

AbstractMamiellophyceae (unicellular green algae) are a key phytoplankton group in coastal waters. Although extensively studied over the last 20 years, the overall oceanic distribution of the major species/clades is still poorly known. To address this problem, we analyzed the 2014 Ocean Sampling Day (OSD) metabarcoding dataset providing sequences from the V4 hypervariable region of the 18S rRNA gene for 157 samples collected at 143 mostly coastal stations. Mamiellophyceae were found at nearly all OSD stations and represented 55% of the green microalgae (Chlorophyta) reads. We performed phylogenetic analyses of unique OSD metabarcodes (amplicon single variants, ASVs) and GenBank reference sequences from cultures and from the environment, focusing on the four most represented genera: Ostreococcus (45% of the Mamiellophyceae reads), Micromonas (34%), Bathycoccus (10%) and Mantoniella (8.7%). These analyses uncovered novel diversity within each genus except Bathycoccus. In Ostreococcus, a new clade (E) was the second most represented clade after Ostreococcus “lucimarinus”. Micromonas could be separated into nine clades, exceeding the six species and candidate species already described. Finally, we found two new environmental clades within Mantoniella. Each Mamiellophyceae clade had a specific distribution in the OSD dataset suggesting that they are adapted to different ecological niches.
Morpho-mechanics of human collagen superstructures revealed by all-optical correlative micro-spectroscopies
Authors: Mercatelli Raffaella , Mattana Sara , Capozzoli Laura , Ratto Fulvio , Rossi Francesca , Pini Roberto , Fioretto Daniele , Pavone Francesco Saverio , Caponi Silvia , Cicchi Riccardo 
Published: March 2019

AbstractIn every biological tissue, morphological and topological properties strongly affect its mechanical features and behaviour, so that ultrastructure, composition and mechanical parameters are intimately connected. Overall, it is their correct interplay that guarantees the tissue functionality. The development of experimental methods able to correlate these properties would open new opportunities both in the biological and the biomedical fields. Here, we report a correlative study intended to map supramolecular morphology, biochemical composition and viscoelastic parameters of collagen by all-optical microscopies. In particular, using human corneal tissue as a benchmark, we correlate Second-Harmonic Generation maps with mechanical and biochemical imaging obtained by Brillouin and Raman micro-spectroscopy. The study highlights how subtle variations in supramolecular organization originate the peculiar mechanical behavior of different subtypes of corneal lamellae. The presented methodology paves the way to the non-invasive assessment of tissue morpho-mechanics in biological as well as synthetic materials.
Red-skewed Kα iron lines in GX 13+1
Authors: Maiolino T. , Laurent P. , Titarchuk L. , Orlandini M. , Frontera F. 
Published: March 2019

Context. Broad, asymmetric, and red-skewed Fe Kα emission lines have been observed in the spectra of low-mass X-ray binaries hosting neutron stars (NSs) as a compact object. Because more than one model is able to describe these features, the explanation of where and how the red-skewed Fe lines are produced is still a matter of discussion. It is broadly accepted that the shape of the Fe Kα line is strongly determined by the special and general relativistic effects occurring in the innermost part of the accretion disk. In this relativistic framework, the Fe fluorescent lines are produced in the innermost part of the accretion disk by reflection of hard X-ray photons coming from the central source (corona and/or NS surface). We developed an alternative and nonrelativistic model, called the WINDLINE model, that is capable to describe the Fe line features. In this nonrelativistic framework, the line photons are produced at the bottom of a partly ionized outflow (wind) shell as a result of illumination by the continuum photons coming from the central source. In this model the red-skewness of the line profile is explained by repeated electron scattering of the photons in a diverging outflow.
Aims. Examining the asymmetry of the fluorescent Fe K emission line evident in the XMM-Newton EPIC-pn spectra of the NS source GX 13+1, we aim to distinguish between the two line models. Because GX 13+1 is a well-known disk-wind source, it is a perfect target for testing the WINDLINE model and compare the spectral fits between the relativistic and nonrelativistic line models.
Methods. We used two XMM-Newton EPIC-pn observations in which the Fe line profiles were previously reported in the literature. These observations are not strongly affected by pile-up, and the Fe emission lines appear very strong and red-skewed. In order to access the goodness of the fit and distinguish between the two line models, we used the run-test statistical method in addition to the canonical χ2 statistical method.
Results. The DISKLINE and WINDLINE models both fit the asymmetric Fe line well that is present in the XMM-Newton energy spectra of GX 13+1. From a statistical point of view, for the two observations we analyzed, the run-test was not able to distinguish between the two Fe line models, at 5% significance level.
Genetics of Nonalcoholic Fatty Liver Disease: From Pathogenesis to Therapeutics
Authors: Sookoian Silvia , Pirola Carlos 
Published: March 2019

AbstractHere, the authors review the remarkable genetic discoveries that have illuminated the biology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). The authors integrate genes associated with NAFLD and NASH into regulatory pathways to elucidate the disease pathogenesis. They review the evidence for molecular mediators of chronic liver damage, which suggests that convergent pathophenotypes, including inflammation and fibrosis, share common genetic modifiers. They further demonstrate that genes involved in the genetic susceptibility of NAFLD and NASH participate in cross-phenotype associations with diseases of the metabolic syndrome, including type 2 diabetes, obesity, and cardiovascular disease. However, immune-related loci associated with NAFLD and NASH exhibit some level of pleiotropy influencing disparate phenotypes, such as premature birth or sepsis. They finally focus on the translation of current genetic knowledge of NAFLD and NASH toward precision medicine. They provide evidence of genetic findings that can be leveraged to identify therapeutic targets.