bluuebunny/crossref_metadata_2025_split huggingface dataset:
EGFR feedback-inhibition by Ran-binding protein 6 is disrupted in cancer
Authors: Oldrini Barbara , Hsieh Wan-Ying , Erdjument-Bromage Hediye , Codega Paolo , Carro Maria Stella , Curiel-García Alvaro , Campos Carl , Pourmaleki Maryam , Grommes Christian , Vivanco Igor , Rohle Daniel , Bielski Craig M. , Taylor Barry S. , Hollmann Travis J. , Rosenblum Marc , Tempst Paul , Blenis John , Squatrito Massimo , Mellinghoff Ingo K. 
Published: December 2017

AbstractTransport of macromolecules through the nuclear pore by importins and exportins plays a critical role in the spatial regulation of protein activity. How cancer cells co-opt this process to promote tumorigenesis remains unclear. The epidermal growth factor receptor (EGFR) plays a critical role in normal development and in human cancer. Here we describe a mechanism of EGFR regulation through the importin β family member RAN-binding protein 6 (RanBP6), a protein of hitherto unknown functions. We show that RanBP6 silencing impairs nuclear translocation of signal transducer and activator of transcription 3 (STAT3), reduces STAT3 binding to the EGFR promoter, results in transcriptional derepression of EGFR, and increased EGFR pathway output. Focal deletions of the RanBP6 locus on chromosome 9p were found in a subset of glioblastoma (GBM) and silencing of RanBP6 promoted glioma growth in vivo. Our results provide an example of EGFR deregulation in cancer through silencing of components of the nuclear import pathway.
Two-dimensional topological superconductivity in Pb/Co/Si(111)
Authors: Ménard Gerbold C. , Guissart Sébastien , Brun Christophe , Leriche Raphaël T. , Trif Mircea , Debontridder François , Demaille Dominique , Roditchev Dimitri , Simon Pascal , Cren Tristan 
Published: December 2017

AbstractJust like insulators can present topological phases characterized by Dirac edge states, superconductors can exhibit topological phases characterized by Majorana edge states. In particular, one-dimensional topological superconductors are predicted to host zero-energy Majorana fermions at their extremities. By contrast, two-dimensional superconductors have a one-dimensional boundary which would naturally lead to propagating Majorana edge states characterized by a Dirac-like dispersion. In this paper we present evidences of one-dimensional dispersive in-gap edge states surrounding a two-dimensional topological superconducting domain consisting of a monolayer of Pb covering magnetic Co–Si islands grown on Si(111). We interpret the measured dispersive in-gap states as a spatial topological transition with a gap closure. Our method could in principle be generalized to a large variety of heterostructures combining a Rashba superconductor with a magnetic layer in order to be used as a platform for engineering topological quantum phases.
Migratory dendritic cells acquire and present lymphatic endothelial cell-archived antigens during lymph node contraction
Authors: Kedl Ross M. , Lindsay Robin S. , Finlon Jeffrey M. , Lucas Erin D. , Friedman Rachel S. , Tamburini Beth A. Jirón 
Published: December 2017

AbstractAntigens derived from viral infection or vaccination can persist within a host for many weeks after resolution of the infection or vaccine responses. We previously identified lymphatic endothelial cells (LEC) as the repository for this antigen archival, yet LECs are unable to present their archived antigens to CD8+T cells, and instead transfer their antigens to CD11c+antigen-presenting cells (APC). Here we show that the exchange of archived antigens between LECs and APCs is mediated by migratory dendritic cells (DC). After vaccination, both migratory basic leucine zipper ATF-like transcription factor 3 (BatF3)-dependent and BatF3-independent DCs are responsible for antigen exchange and cross-presentation. However, exchange of archived viral antigens is mediated only by BatF3-dependent migratory DCs potentially acquiring apoptotic LECs. In conclusion, LEC-archived antigens are exchanged with migratory DCs, both directly and through LEC apoptosis, to cross-present archived antigens to circulating T cells.
Estimation of immune cell content in tumour tissue using single-cell RNA-seq data
Authors: Schelker Max , Feau Sonia , Du Jinyan , Ranu Nav , Klipp Edda , MacBeath Gavin , Schoeberl Birgit , Raue Andreas 
Published: December 2017

AbstractAs interactions between the immune system and tumour cells are governed by a complex network of cell–cell interactions, knowing the specific immune cell composition of a solid tumour may be essential to predict a patient’s response to immunotherapy. Here, we analyse in depth how to derive the cellular composition of a solid tumour from bulk gene expression data by mathematical deconvolution, using indication-specific and cell type-specific reference gene expression profiles (RGEPs) from tumour-derived single-cell RNA sequencing data. We demonstrate that tumour-derived RGEPs are essential for the successful deconvolution and that RGEPs from peripheral blood are insufficient. We distinguish nine major cell types, as well as three T cell subtypes. Using the tumour-derived RGEPs, we can estimate the content of many tumours associated immune and stromal cell types, their therapeutically relevant ratios, as well as an improved gene expression profile of the malignant cells.
Single-cell RNA-sequencing uncovers transcriptional states and fate decisions in haematopoiesis
Authors: Athanasiadis Emmanouil I. , Botthof Jan G. , Andres Helena , Ferreira Lauren , Lio Pietro , Cvejic Ana 
Published: December 2017

AbstractThe success of marker-based approaches for dissecting haematopoiesis in mouse and human is reliant on the presence of well-defined cell surface markers specific for diverse progenitor populations. An inherent problem with this approach is that the presence of specific cell surface markers does not directly reflect the transcriptional state of a cell. Here, we used a marker-free approach to computationally reconstruct the blood lineage tree in zebrafish and order cells along their differentiation trajectory, based on their global transcriptional differences. Within the population of transcriptionally similar stem and progenitor cells, our analysis reveals considerable cell-to-cell differences in their probability to transition to another committed state. Once fate decision is executed, the suppression of transcription of ribosomal genes and upregulation of lineage-specific factors coordinately controls lineage differentiation. Evolutionary analysis further demonstrates that this haematopoietic programme is highly conserved between zebrafish and higher vertebrates.
Eml1 loss impairs apical progenitor spindle length and soma shape in the developing cerebral cortex
Authors: Bizzotto Sara , Uzquiano Ana , Dingli Florent , Ershov Dmitry , Houllier Anne , Arras Guillaume , Richards Mark , Loew Damarys , Minc Nicolas , Croquelois Alexandre , Houdusse Anne , Francis Fiona 
Published: December 2017

AbstractThe ventricular zone (VZ) of the developing cerebral cortex is a pseudostratified epithelium that contains progenitors undergoing precisely regulated divisions at its most apical side, the ventricular lining (VL). Mitotic perturbations can contribute to pathological mechanisms leading to cortical malformations. The HeCo mutant mouse exhibits subcortical band heterotopia (SBH), likely to be initiated by progenitor delamination from the VZ early during corticogenesis. The causes for this are however, currently unknown. Eml1, a microtubule (MT)-associated protein of the EMAP family, is impaired in these mice. We first show that MT dynamics are perturbed in mutant progenitor cells in vitro. These may influence interphase and mitotic MT mechanisms and indeed, centrosome and primary cilia were altered and spindles were found to be abnormally long in HeCo progenitors. Consistently, MT and spindle length regulators were identified in EML1 pulldowns from embryonic brain extracts. Finally, we found that mitotic cell shape is also abnormal in the mutant VZ. These previously unidentified VZ characteristics suggest altered cell constraints which may contribute to cell delamination.
Molecular cloning of novel transcripts of human kallikrein-related peptidases 5, 6, 7, 8 and 9 (KLK5 – KLK9), using Next-generation sequencing
Authors: Adamopoulos Panagiotis G. , Kontos Christos K. , Scorilas Andreas 
Published: December 2017

AbstractAlternative splicing of cancer-related genes is a common cellular mechanism accounting for cancer cell transcriptome complexity and affecting cell cycle control, proliferation, apoptosis, angiogenesis, invasion, and metastasis. In this study, we describe the discovery and molecular cloning of thirty novel transcripts of the human KLK5, KLK6, KLK7, KLK8 and KLK9 genes, using 3′ rapid amplification of cDNA ends (3′ RACE) and NGS technology, as well as their expression analysis in many established cell lines, originating from several distinct cancerous and normal tissues. Extensive bioinformatic analysis revealed novel splice variants of these five members of the KLK family, comprising entirely new exons, previously unknown boundaries of the already annotated exons (extensions and truncations) as well as alternative splicing events between these exons. Nested RT-PCR in a panel of human cell lines originating from seventeen cancerous and two normal tissues with the use of variant-specific pairs of primers was carried out for expression analysis of these novel splice variants, and Sanger sequencing of the respective amplicons confirmed our NGS results. Given that some splice variants of KLK family members possess clinical value, novel alternatively spliced transcripts appear as new candidate biomarkers for diagnostic and/or prognostic purposes and as targets for therapeutic strategies.
Comparative genome analysis of the vineyard weed endophyte Pseudomonas viridiflava CDRTc14 showing selective herbicidal activity
Authors: Samad Abdul , Antonielli Livio , Sessitsch Angela , Compant Stéphane , Trognitz Friederike 
Published: December 2017

AbstractMicrobes produce a variety of secondary metabolites to be explored for herbicidal activities. We investigated an endophyte Pseudomonas viridiflava CDRTc14, which impacted growth of its host Lepidium draba L., to better understand the possible genetic determinants for herbicidal and host-interaction traits. Inoculation tests with a variety of target plants revealed that CDRTc14 shows plant-specific effects ranging from beneficial to negative. Its herbicidal effect appeared to be dose-dependent and resembled phenotypically the germination arrest factor of Pseudomonas fluorescens WH6. CDRTc14 shares 183 genes with the herbicidal strain WH6 but the formylaminooxyvinylglycine (FVG) biosynthetic genes responsible for germination arrest of WH6 was not detected. CDRTc14 showed phosphate solubilizing ability, indole acetic acid and siderophores production in vitro and harbors genes for these functions. Moreover, genes for quorum sensing, hydrogen cyanide and ACC deaminase production were also found in this strain. Although, CDRTc14 is related to plant pathogens, we neither found a complete pathogenicity island in the genome, nor pathogenicity symptoms on susceptible plant species upon CDRTc14 inoculation. Comparison with other related genomes showed several unique genes involved in abiotic stress tolerance in CDRTc14 like genes responsible for heavy metal and herbicide resistance indicating recent adaptation to plant protection measures applied in vineyards.
Understanding population structure and historical demography of Litsea auriculata (Lauraceae), an endangered species in east China
Authors: Geng Qifang , Sun Lin , Zhang Peihua , Wang Zhongsheng , Qiu Yingxiong , Liu Hong , Lian Chunlan 
Published: December 2017

AbstractDetecting how historical and contemporary factors contribute to genetic divergence and genetic structure is a central question in ecology and evolution. We examine this question by intergrating population genetics with ecological niche modelling ofLitsea auriculata(Lauraceae), which is endangered and native to east China. Geographical and environmental factors including climatic fluctuations since the last glacial maximum (LGM) have also contribute to population demography and patterns of genetic structure.L.auriculatapopulations underwent expansion after divergence and dramatically decreased to the current small size with relative population bottlenecks due to climate changes. Populations separated by physical geographical barrier including geographic distance and Yangtze River, as a result contemporary gene flow amongL.auriculatapopulations showed drastic declines in comparison with historical gene flow, resulting in a high level of population divergence. Thus, patterns of genetic structure ofL.auriculatacan result from both geographic and environmental factors including climate changes. This information is helpful in forming conservation strategies forL.auriculatain China.
Identification of a gene signature for discriminating metastatic from primary melanoma using a molecular interaction network approach
Authors: Metri Rahul , Mohan Abhilash , Nsengimana Jérémie , Pozniak Joanna , Molina-Paris Carmen , Newton-Bishop Julia , Bishop David , Chandra Nagasuma 
Published: December 2017

AbstractUnderstanding the biological factors that are characteristic of metastasis in melanoma remains a key approach to improving treatment. In this study, we seek to identify a gene signature of metastatic melanoma. We configured a new network-based computational pipeline, combined with a machine learning method, to mine publicly available transcriptomic data from melanoma patient samples. Our method is unbiased and scans a genome-wide protein-protein interaction network using a novel formulation for network scoring. Using this, we identify the most influential, differentially expressed nodes in metastatic as compared to primary melanoma. We evaluated the shortlisted genes by a machine learning method to rank them by their discriminatory capacities. From this, we identified a panel of 6 genes, ALDH1A1, HSP90AB1, KIT, KRT16, SPRR3 and TMEM45B whose expression values discriminated metastatic from primary melanoma (87% classification accuracy). In an independent transcriptomic data set derived from 703 primary melanomas, we showed that all six genes were significant in predicting melanoma specific survival (MSS) in a univariate analysis, which was also consistent with AJCC staging. Further, 3 of these genes, HSP90AB1, SPRR3 and KRT16 remained significant predictors of MSS in a joint analysis (HR = 2.3, P = 0.03) although, HSP90AB1 (HR = 1.9, P = 2 × 10−4) alone remained predictive after adjusting for clinical predictors.
Ensemble Modeling Approach Targeting Heterogeneous RNA-Seq data: Application to Melanoma Pseudogenes
Authors: Capobianco Enrico , Valdes Camilo , Sarti Samanta , Jiang Zhijie , Poliseno Laura , Tsinoremas Nicolas F. 
Published: December 2017

AbstractWe studied the transcriptome landscape of skin cutaneous melanoma (SKCM) using 103 primary tumor samples from TCGA, and measured the expression levels of both protein coding genes and non-coding RNAs (ncRNAs). In particular, we emphasized pseudogenes potentially relevant to this cancer. While cataloguing the profiles based on the known biotypes, all the employed RNA-Seq methods generated just a small consensus of significant biotypes. We thus designed an approach to reconcile the profiles from all methods following a simple strategy: we selected genes that were confirmed as differentially expressed by the ensemble predictions obtained in a regression model. The main advantages of this approach are: 1) Selection of a high-confidence gene set identifying relevant pathways; 2) Use of a regression model whose covariates embed all method-driven outcomes to predict an averaged profile; 3) Method-specific assessment of prediction power and significance. Furthermore, the approach can be generalized to any biological system for which noisy RNA-Seq profiles are computed. As our analyses concerned bio-annotations of both high-quality protein coding genes and ncRNAs, we considered the associations between pseudogenes and parental genes (targets). Among the candidate targets that were validated, we identified PINK1, which is studied in patients with Parkinson and cancer (especially melanoma).
A neuronal signature of accurate imitative learning in wild-caught songbirds (swamp sparrows, Melospiza georgiana)
Authors: Moseley Dana L. , Joshi Narendra R. , Prather Jonathan F. , Podos Jeffrey , Remage-Healey Luke 
Published: December 2017

AbstractIn humans and other animals, behavioural variation in learning has been associated with variation in neural features like morphology and myelination. By contrast, it is essentially unknown whether cognitive performance scales with electrophysiological properties of individual neurons. Birdsong learning offers a rich system to investigate this topic as song acquisition is similar to human language learning. Here, we address the interface between behavioural learning and neurophysiology in a cohort of wild-caught, hand-reared songbirds (swamp sparrows, Melospiza georgiana). We report the discovery in the forebrain HVC of sensorimotor ‘bridge’ neurons that simultaneously and selectively represent two critical learning-related schemas: the bird’s own song, and the specific tutor model from which that song was copied. Furthermore, the prevalence and response properties of bridge neurons correlate with learning ability – males that copied tutor songs more accurately had more bridge neurons. Our results are consistent with the hypothesis that accurate imitative learning depends on a successful bridge, within single cortical neurons, between the representation of learning models and their sensorimotor copies. Whether such bridge neurons are a necessary mechanism for accurate learning or an outcome of learning accuracy is unknown at this stage, but can now be addressed in future developmental studies.
Bis(monoacylglycero)phosphate lipids in the retinal pigment epithelium implicate lysosomal/endosomal dysfunction in a model of Stargardt disease and human retinas
Authors: Anderson David M. G. , Ablonczy Zsolt , Koutalos Yiannis , Hanneken Anne M. , Spraggins Jeffrey M. , Calcutt M. Wade , Crouch Rosalie K. , Caprioli Richard M. , Schey Kevin L. 
Published: December 2017

AbstractStargardt disease is a juvenile onset retinal degeneration, associated with elevated levels of lipofuscin and its bis-retinoid components, such as N-retinylidene-N-retinylethanolamine (A2E). However, the pathogenesis of Stargardt is still poorly understood and targeted treatments are not available. Utilizing high spatial and high mass resolution matrix assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS), we determined alterations of lipid profiles specifically localized to the retinal pigment epithelium (RPE) in Abca4
−/−
Stargardt model mice compared to their relevant background strain. Extensive analysis by LC-MS/MS in both positive and negative ion mode was required to accurately confirm the identity of one highly expressed lipid class, bis(monoacylgylercoro)phosphate (BMP) lipids, and to distinguish them from isobaric species. The same BMP lipids were also detected in the RPE of healthy human retina. BMP lipids have been previously associated with the endosomal/lysosomal storage diseases Niemann-Pick and neuronal ceroid lipofuscinosis and have been reported to regulate cholesterol levels in endosomes. These results suggest that perturbations in lipid metabolism associated with late endosomal/lysosomal dysfunction may play a role in the pathogenesis of Stargardt disease and is evidenced in human retinas.
Whole-genome sequencing and SNV genotyping of ‘Nebbiolo’ (Vitis vinifera L.) clones
Authors: Gambino Giorgio , Dal Molin Alessandra , Boccacci Paolo , Minio Andrea , Chitarra Walter , Avanzato Carla Giuseppina , Tononi Paola , Perrone Irene , Raimondi Stefano , Schneider Anna , Pezzotti Mario , Mannini Franco , Gribaudo Ivana , Delledonne Massimo 
Published: December 2017

Abstract‘Nebbiolo’ (Vitis vinifera) is among the most ancient and prestigious wine grape varieties characterised by a wide genetic variability exhibited by a high number of clones (vegetatively propagated lines of selected mother plants). However, limited information is available for this cultivar at the molecular and genomic levels. The whole-genomes of three ‘Nebbiolo’ clones (CVT 71, CVT 185 and CVT 423) were re-sequenced and a de novo transcriptome assembly was produced. Important remarks about the genetic peculiarities of ‘Nebbiolo’ and its intra-varietal variability useful for clonal identification were reported. In particular, several varietal transcripts identified for the first time in ‘Nebbiolo’ were disease resistance genes and single-nucleotide variants (SNVs) identified in ‘Nebbiolo’, but not in other cultivars, were associated with genes involved in the stress response. Ten newly discovered SNVs were successfully employed to identify some periclinal chimeras and to classify 98 ‘Nebbiolo’ clones in seven main genotypes, which resulted to be linked to the geographical origin of accessions. In addition, for the first time it was possible to discriminate some ‘Nebbiolo’ clones from the others.
Laser-induced blurring of molecular structure information in high harmonic spectroscopy
Authors: Risoud François , Lévêque Camille , Labeye Marie , Caillat Jérémie , Maquet Alfred , Salières Pascal , Taïeb Richard , Shaaran Tahir 
Published: December 2017

AbstractHigh harmonic spectroscopy gives access to molecular structure with Angström resolution. Such information is encoded in the destructive interferences occurring between the harmonic emissions from the different parts of the molecule. By solving the time-dependent Schrödinger equation, either numerically or with the molecular strong-field approximation, we show that the electron dynamics in the emission process generally results in a strong spectral smoothing of the interferences, blurring the structural information. However we identify specific generation conditions where they are unaffected. These findings have important consequences for molecular imaging and orbital tomography using high harmonic spectroscopy.
Artemisia annua extract prevents ovariectomy-induced bone loss by blocking receptor activator of nuclear factor kappa-B ligand-induced differentiation of osteoclasts
Authors: Lee Sun Kyoung , Kim Hyungkeun , Park Junhee , Kim Hyun-Jeong , Kim Ki Rim , Son Seung Hwa , Park Kwang-Kyun , Chung Won-Yoon 
Published: December 2017

AbstractThe activities of osteoclasts and osteoblasts are balanced to maintain normal bone density. Many pathological conditions cause osteoclastic bone resorption in excess of osteoblastic bone formation, resulting in osteoporosis. We found that oral administration of Artemisia annua ethanol extract (AaE) or major components, artemisinin and arteannuin B, to ovariectomized (OVX) mice prevented bone loss, as verified by examining three-dimensional images and bone morphometric parameters derived from microcomputed tomography analysis, as well as serum levels of bone turnover markers and proinflammatory cytokines. The administered doses were not toxic to the liver or kidney and showed promising effects that were comparable to those of 17β-estradiol treatment. At non-cytotoxic concentrations, AaE and active components, artemisinin, artemisinic acid, and arteannuin B, potently inhibited receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis and the formation of osteoclast-mediated resorption pits. Furthermore, AaE, artemisinin, and arteannuin B remarkably reduced the expression of the c-Fos and NFATc1 transcription factors, which play critical roles in RANKL-induced osteoclast differentiation. Taken together, the in vivo anti-osteoporotic activity of AaE may be derived from the anti-osteoclastic and anti-bone resorptive activities of its active components. AaE has beneficial applications for the prevention and inhibition of osteoporosis and osteoclast-mediated bone diseases.