bluuebunny/crossref_metadata_2025_split huggingface dataset:
When tension is exciting: an EEG exploration of excitement in music
Authors: Turrell Amelia , Halpern Andrea R , Javadi Amir-Homayoun 
Published: May 2019

AbstractMusic powerfully affects people’s emotions. In particular, moments of tension and deviation in musical features, including frequency, pitch, and rhythm (known as a Drop), are associated with positive emotions. However, the neuro-correlates of Drops emotive effects have never been explored. Thirty-six participants listened to music pieces containing a Drop, while undergoing continuous EEG, and rated felt excitement. Source reconstruction of EEG data showed significantly different activity in five brain regions before and after Drops: pre- and post-central gyri (PreCG and PostCG), and precuneus (PCUN) were more active before Drops and the inferior frontal gyrus (IFG), and middle frontal gyrus (MFG) were more active after Drops. Importantly, activity in the IFG and MFG showed a strong correlation with subjective excitement ratings during Drop apprehension. These results suggest expectancy is important to the induction of musical emotions, in agreement with the ITPRA theory. Specifically, when Drops are expected but do not occur immediately, moderate tension is induced. Strong positive emotions then ensue when expected deviations finally occur, due to contrastive valence. This is reflected in significant brain activity for regions associated with high arousing, pleasurable emotions, such as excitement.
Stereomotion processing in the non-human primate brain
Authors: Héjja-Brichard Yseult , Rima Samy , Rapha Emilie , Durand Jean-Baptiste , Cottereau Benoit R. 
Published: May 2019

AbstractThe cortical areas that process disparity-defined motion-in-depth (i.e. cyclopean stereomotion) were characterised with functional magnetic resonance imaging in two awake, behaving macaques. The experimental protocol was similar to previous human neuroimaging studies. We contrasted the responses to dynamic random-dot patterns that continuously changed their binocular disparity over time with those to a control condition that shared the same properties, except that the temporal frames were shuffled. A whole-brain voxel-wise analysis revealed that in all four cortical hemispheres, three areas showed consistent sensitivity to cyclopean stereomotion. Two of them were localised respectively in the lower bank of the superior temporal sulcus (CSMSTS) and on the neighbouring infero-temporal gyrus (CSMITG). The third area was situated in the posterior parietal cortex (CSMPPC). Additional ROIs-based analyses within retinotopic areas defined in both animals indicated weaker but significant responses to cyclopean stereomotion within the MT cluster (most notably in areas MSTv and FST). Altogether, our results are in agreement with previous findings in both human and macaque and suggest that the cortical networks that process cyclopean stereomotion is relatively well preserved between the two primate species.
Active Poroelastic Two-Phase Model for the Motion of Physarum Microplasmodia
Authors: Kulawiak Dirk Alexander , Löber Jakob , Bär Markus , Engel Harald 
Published: May 2019

AbstractThe onset of self-organized motion is studied in a poroelastic two-phase model with free boundaries for Physarum microplasmodia (MP). In the model, an active gel phase is assumed to be interpenetrated by a passive fluid phase on small length scales. A feedback loop between calcium kinetics, mechanical deformations, and induced fluid flow gives rise to pattern formation and the establishment of an axis of polarity. Altogether, we find that the calcium kinetics that breaks the conservation of the total calcium concentration in the model and a nonlinear friction between MP and substrate are both necessary ingredients to obtain an oscillatory movement with net motion of the MP. By numerical simulations in one spatial dimension, we find two different types of oscillations with net motion as well as modes with time-periodic or irregular switching of the axis of polarity. The more frequent type of net motion is characterized by mechano-chemical waves traveling from the front towards the rear. The second type is characterized by mechano-chemical waves that appear alternating from the front and the back. While both types exhibit oscillatory forward and backward movement with net motion in each cycle, the trajectory and gel flow pattern of the second type are also similar to recent experimental measurements of peristaltic MP motion. We found moving MPs in extended regions of experimentally accessible parameters, such as length, period and substrate friction strength. Simulations of the model show that the net speed increases with the length, provided that MPs are longer than a critical length of ≈ 120 µm. Both predictions are in line with recent experimental observations.
Analyzing the weak dimerization of a cellulose binding module by sedimentation velocity experiments
Authors: Fedorov Dmitrii , Batys Piotr , Sammalkorpi Maria , Linder Markus B. 
Published: May 2019

AbstractCellulose binding modules (CBMs) are found widely in different proteins that act on cellulose. Because they allow a very easy way of binding recombinant proteins to cellulose, they have become widespread in many biotechnological applications involving cellulose. One commonly used variant is the CBMCipAfromClostridium thermocellum. Here we studied the dimerization of CBMCipA, because we were interested if its solution behavior could have an impact on its use in biotechnical applications. As the principal approach, we used sedimentation velocity analytical ultracentrifugation. To enhance our understanding of the possible interactions, we used molecular dynamics simulations. By analysis of the sedimentation velocity data using a discrete model genetic algorithm we found that the CBMCipAshows a weak dimerization interaction with a dissociation constantKDof about 87 μM. As theKDof CBMCipAbinding to cellulose is about 0.6 μM, we conclude that the dimerization is unlikely to affect cellulose binding. However, at the high concentrations used in some applications of the CMBCipA, its dimerization is likely to have an effect on its solution behavior. The work shows that analytical ultracentrifugation is a very efficient tool to analyze this type of weak interactions. Moreover, we provide here a protocol for data analysis in the program Ultrascan for determining dissociation constants by sedimentation velocity experiments.
Addiction of mesenchymal phenotypes on the FGF/FGFR axis in oral squamous cell carcinoma cells
Authors: Osada Asami Hotta , Endo Kaori , Kimura Yujiro , Sakamoto Kei , Nakamura Ryosuke , Sakamoto Kaname , Ueki Koichiro , Yoshizawa Kunio , Miyazawa Keiji , Saitoh Masao 
Published: May 2019

AbstractThe epithelial–mesenchymal transition (EMT) is a crucial morphological event that occurs during epithelial tumor progression. ZEB1/2 are EMT transcription factors that are positively correlated with EMT phenotypes and breast cancer aggressiveness. ZEB1/2 regulate the alternative splicing and hence isoform switching of fibroblast growth factor receptors (FGFRs) by repressing the epithelial splicing regulatory proteins, ESRP1 and ESRP2. Here, we show that the mesenchymal-like phenotypes of oral squamous cell carcinoma (OSCC) cells are dependent on autocrine FGF–FGFR signaling. Mesenchymal-like OSCC cells express low levels of ESRP1/2 and high levels of ZEB1/2, resulting in constitutive expression of the IIIc-isoform of FGFR, FGFR(IIIc). By contrast, epithelial-like OSCC cells showed opposite expression profiles for these proteins and constitutive expression of the IIIb-isoform of FGFR2, FGFR2(IIIb). Importantly, ERK was constitutively phosphorylated through FGFR1(IIIc), which was activated by factors secreted autonomously by mesenchymal-like OSCC cells and involved in sustained high-level expression of ZEB1. Antagonizing FGFR1 with either an inhibitor or siRNAs considerably repressed ZEB1 expression and restored epithelial-like traits. Therefore, autocrine FGF–FGFR(IIIc) signaling appears to be responsible for sustaining ZEB1/2 at high levels and the EMT phenotype in OSCC cells.
Aberrant DNA methylation of miRNAs in Fuchs endothelial corneal dystrophy
Authors: Pan Peipei , Weisenberger Daniel J. , Zheng Siyu , Wolf Marie , Hwang David G. , Rose-Nussbaumer Jennifer R. , Jurkunas Ula V. , Chan Matilda F. 
Published: May 2019

AbstractHomeostatic maintenance of corneal endothelial cells is essential for maintenance of corneal deturgescence and corneal transparency. In Fuchs endothelial corneal dystrophy (FECD), an accelerated loss and dysfunction of endothelial cells leads to progressively severe visual impairment. An abnormal accumulation of extracellular matrix is a distinctive hallmark of the disease, however the molecular pathogenic mechanisms underlying this phenomenon are not fully understood. We recently reported characteristic patterns of DNA methylation changes in the corneal endothelial cells of patients with FECD. Here, we investigate genome-wide and sequence-specific DNA methylation changes of miRNA genes in corneal endothelial samples derived from patients with FECD. We show that the majority of miRNA genes are hypermethylated at their promoter regions in FECD. More specifically, miR-199B is an extensively hypermethylated miRNA gene at its promoter region and its mature transcript miR-199b-5p was previously found to be almost completely silenced in FECD. Using a cell-based assay, we find that miR-199b-5p directly inhibits the expression of two epithelial mesenchymal transition (EMT)-inducing genes, Snai1 and ZEB1. Taken together, these findings suggest a novel regulatory mechanism of matrix protein production by corneal endothelial cells in which miR-199b-5p hypermethylation leads to its down-regulated expression and thereby the decreased expression of miR-199b-5p target genes, including Snai1 and ZEB1. Our results support miR-199b-5p as a potential therapeutic target to prevent or slow down the progression of FECD disease.Author summaryFuchs endothelial corneal dystrophy (FECD) due to corneal endothelial cell degeneration is one of the most common heritable causes of corneal visual loss and a leading indication for corneal transplantation. The progressive loss of corneal endothelial cells is accompanied by an abnormal deposition of extracellular matrix in the form of guttae. Here we discover that miRNA gene promoters are frequent targets of aberrant DNA methylation in FECD. In particular, we describe a novel epigenetic mechanism used by corneal endothelial cells to regulate extracellular matrix production. We find that miRNA-199b-5p functions as a negative regulator of Snai1 and ZEB1, two zinc finger transcription factors that have been shown to lead to increased production of extracellular matrix proteins. Furthermore, miR-199B was extensively hypermethylated in FECD and its mature transcript miR-199b-5p directly binds to the 3′-UTRs of Snai1 and ZEB1 genes. Ultimately, this may negatively modulate Snai1- and ZEB1-mediated production of extracellular matrix proteins. This work is the first to identify an important role of DNA methylation in the epigenetic regulation of miRNA-target genes in FECD and to describe a potential epigenetic biomarker for the treatment of FECD patients.
Large eQTL meta-analysis reveals differing patterns between cerebral cortical and cerebellar brain regions
Authors: Sieberts Solveig K. , Perumal Thanneer , Carrasquillo Minerva M. , Allen Mariet , Reddy Joseph S. , Hoffman Gabriel E. , Dang Kristen K. , Calley John , Ebert Philip J. , Eddy James , Wang Xue , Greenwood Anna K. , Mostafavi Sara ,   the AMP-AD Consortium,   the CommonMind Consortium (CMC), Omberg Larsson , Peters Mette , Logsdon Benjamin A. , De Jager Philip L. , Ertekin-Taner Nilüfer , Mangravite Lara M. ,   AMP-AD Consortium,   CommonMind Consortium
Published: May 2019

AbstractThe availability of high-quality RNA-sequencing and genotyping data of post-mortem brain collections from consortia such as CommonMind Consortium (CMC) and the Accelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD) Consortium enable the generation of a large-scale brain cis-eQTL meta-analysis. Here we generate cerebral cortical eQTL from 1433 samples available from four cohorts (identifying >4.1 million significant eQTL for >18,000 genes), as well as cerebellar eQTL from 261 samples (identifying 874,836 significant eQTL for >10,000 genes), and provide the results as a community resource. We find substantially improved power in the meta-analysis over individual cohort analyses, particularly in comparison to the Genotype-Tissue Expression (GTEx) Project eQTL. In addition, we observed differences in eQTL patterns between cerebral and cerebellar brain regions. We provide these brain eQTL as a common resource for use across the community in research programs. As a proof of principle for their utility, we apply a colocalization analysis to identify genes underlying the GWAS association peaks for schizophrenia and identify a potentially novel gene colocalization with lncRNA RP11-677M14.2 (posterior probability of colocalization 0.975).
Cellular reprogramming for successful CNS axon regeneration is driven by a temporally changing cast of transcription factors
Authors: Dhara Sumona P. , Rau Andrea , Flister Michael J. , Recka Nicole M. , Laiosa Michael D. , Auer Paul L. , Udvadia Ava J. 
Published: May 2019

AbstractIn contrast to mammals, adult fish display a remarkable ability to fully regenerate central nervous system (CNS) axons, enabling functional recovery from CNS injury. Both fish and mammals normally undergo a developmental downregulation of axon growth activity as neurons mature. Fish are able to undergo damage-induced “reprogramming” through re-expression of genes necessary for axon growth and guidance, however, the gene regulatory mechanisms remain unknown. Here we present the first comprehensive analysis of gene regulatory reprogramming in zebrafish retinal ganglion cells at specific time points along the axon regeneration continuum from early growth to target reinnervation. Our analyses reveal a regeneration program characterized by sequential activation of stage-specific pathways, regulated by a temporally changing cast of transcription factors that bind to stably accessible DNA regulatory regions. Strikingly, we also find a discrete set of regulatory regions that change in accessibility, consistent with higher-order changes in chromatin organization that mark (1) the beginning of regenerative axon growth in the optic nerve, and (2) the re-establishment of synaptic connections in the brain. Together, these data provide valuable insight into the regulatory logic driving successful vertebrate CNS axon regeneration, revealing key gene regulatory candidates for therapeutic development.
Mouse and human microglial phenotypes in Alzheimer’s disease are controlled by amyloid plaque phagocytosis through Hif1α
Authors: Grubman Alexandra , Choo Xin Yi , Chew Gabriel , Ouyang John F. , Sun Guizhi , Croft Nathan P. , Rossello Fernando J. , Simmons Rebecca , Buckberry Sam , Landin Dulce Vargas , Pflueger Jahnvi , Vandekolk Teresa H. , Abay Zehra , Liu Xiaodong , Haynes John M. , McLean Catriona , Williams Sarah , Chai Siew Yeen , Wilson Trevor , Lister Ryan , Pouton Colin W. , Purcell Anthony W. , Rackham Owen J. L. , Petretto Enrico , Polo Jose M. 
Published: May 2019

ABSTRACTThe important role of microglia, the brain’s resident immune cells, in Alzheimer’s disease (AD) is now well recognized, however their molecular and functional diversity and underlying mechanisms still remain controversial. To transcriptionally and functionally characterize the diversity of microglia in AD and aging, we isolated the amyloid plaque-containing (XO4+) and non-containing (XO4−) microglia from an AD mouse model. Transcriptomics analysis unveiled independent transcriptional trajectories in ageing and AD. XO4+ microglial transcriptomes linked plaque phagocytosis to altered expression of bona fide late onset AD genetic risk factors. We further revealed that the XO4+ transcriptional program is present in a subset of human microglia from AD patients and is a direct and reversible consequence of Aβ plaque phagocytosis. Conversely, XO4− microglia in AD displayed an accelerated ageing signature and contained more intracellular post synaptic material than plaque-containing microglia, despite reduced active synaptosome phagocytosis. Mechanistically, we predicted HIF1α as a core regulator of the XO4−/XO4+ axis, and further validated the mechanism in vitro using human stem cell-derived microglia like cells and primary human microglia. Together these findings unveiled the molecular mechanism underpinning the functional diversity of microglia in AD, providing opportunities to develop treatments targeted at subset specific manipulation of the microglial niche.
The soursop genome and comparative genomics of basal angiosperms provide new insights on evolutionary incongruence
Authors: Strijk Joeri S. , Hinsinger Damien D. , Roeder Mareike M. , Chatrou Lars W. , Couvreur Thomas L. P. , Erkens Roy H. J. , Sauquet Hervé , Pirie Michael D. , Thomas Daniel C. , Cao Kunfang 
Published: May 2019

AbstractDeep relationships and the sequence of divergence among major lineages of angiosperms (magnoliids, monocots and eudicots) remain ambiguous and differ depending on analytical approaches and datasets used. Complete genomes potentially provide opportunities to resolve these uncertainties, but two recently published magnoliid genomes instead deliver further conflicting signals. To disentangle key angiosperm relationships, we report a high-quality draft genome for the soursop (Annona muricata, Annonaceae). We reconstructed phylogenomic trees and show that the soursop represents a genomic mosaic supporting different histories, with scaffolds almost exclusively supporting single topologies. However, coalescent methods and a majority of genes support magnoliids as sister to monocots and eudicots, where previous whole genome-based studies remained inconclusive. This result is clear and consistent with recent studies using plastomes. The soursop genome highlights the need for more early diverging angiosperm genomes and critical assessment of the suitability of such genomes for inferring evolutionary history.
Detecting Novel Sequence Signals in Targeting Peptides Using Deep Learning
Authors: Almagro Armenteros J.J. , Salvatore M. , Emanuelsson O. , Winther O. , von Heijne G. , Elofsson A. , Nielsen H. 
Published: May 2019

AbstractIn bioinformatics, machine learning methods have been used to predict features embedded in the sequences. In contrast to what is generally assumed, machine learning approaches can also provide new insights into the underlying biology. Here, we demonstrate this by presenting TargetP 2.0, a novel state of art method to identify N-terminal sorting signals, which direct proteins to the secretory pathway, mitochondria and chloroplasts or other plastids.By examining the strongest signals from the attention layer in the network, we find that the second residue in the protein, i.e. the one following the initial methionine, has a strong influence on the classification. When subsequently examining all targeting peptides, we observe that two-thirds of chloroplast and thylakoid transit peptides have an alanine in position two, but only 20% of other plant proteins. Further highlighting the importance of the second residue, we also note that in fungi and single-celled eukaryotes, less than 30% of the targeting peptides have an amino acid that allows the removal of the N-terminal methionine compared with 60% for the proteins without targeting peptide.TargetP 2.0 is available at http://www.cbs.dtu.dk/services/TargetP-2.0/index.php
Topographic preservation of functional connectivity among the association areas in the human cerebral cortex
Authors: Koide-Majima Naoko , Nishimoto Shinji 
Published: May 2019

SummaryIn the human sensorimotor cortex, some long-range corticocortical connections appear to preserve a fine-scale topology, in which physically close locations in the cortical region are functionally connected to physically close locations in other cortical regions. However, little is known about whether such topography preservation is unique to the sensorimotor areas or is general across other cortical areas. To investigate this question, we measured voxel-level functional connectivity using functional magnetic resonance imaging (fMRI) and visualized the fine-scale spatial organization of the connectivity patterns across the cortical surface. We found topographical preservation across regions, including the default mode network. Our results suggest that the topographical preservation of functional connectivity is not restricted to the sensorimotor cortex but also occurs in the association cortex.
Synergy pattern of short cationic antimicrobial peptides against multidrug-resistantPseudomonas aeruginosa
Authors: Ruden Serge , Rieder Annika , Schwartz Thomas , Mikut Ralf , Hilpert Kai 
Published: May 2019

AbstractWith the rise of various multi-drug resistance pathogenic bacteria, worldwide health care is under pressure to respond. Conventional antibiotics are failing and the development of novel classes or alternative strategies is a major priority. Antimicrobial peptides (AMPs) can not only kill multi-drug resistant bacteria, but also can be used synergistically with conventional antibiotics. We selected 30 short AMPs from different origins and measured their synergy in combination with Polymyxin B, Piperacillin, Ceftazidime, Cefepime, Meropenem, Imipenem, Tetracycline, Erythromycin, Kanamycin, Tobramycin, Amikacin, Gentamycin, and Ciprofloxacin. In total 403 unique combinations were tested against a multi-drug resistantPseudomonas aeruginosaisolate (PA910). As a measure of the synergistic effects, fractional inhibitory concentrations (FICs) were determined using microdilution assays with FICs ranges between 0.25 and 2. A high number of combinations between peptides and Polymyxin B, Erythromycin and Tetracycline were found to be synergistic. Novel variants of Indolicidin also showed a high frequency in synergist interaction.
An aphid effector promotes barley susceptibility through suppression of defence gene expression
Authors: Escudero-Martinez Carmen , Rodriguez Patricia A. , Santos Pablo A. , Stephens Jennifer , Bos Jorunn I.B. 
Published: May 2019

AbstractAphids secrete diverse repertoires of effectors into their hosts to promote the infestation process. While “omics”-approaches facilitated the identification and comparison of effector repertoires from a number of aphid species, the functional characterization of these proteins has been limited to dicot (model) plants. The bird cherry-oat aphid Rhopalosiphum padi is a pest of cereal crops, including barley. Here, we extended efforts to characterize aphid effectors with regards to their role in promoting susceptibility to the R. padi-barley interaction. We selected 3 R. padi effectors based on sequences similarity to previously characterized M. persicae effectors and assessed their subcellular localisation, expression, and role in promoting plant susceptibility. Expression of R. padi effectors RpC002 and Rp1 in transgenic barley lines enhanced plant susceptibility to R. padi but not M. persicae, for which barley is a poor host. Characterization of Rp1 transgenic barley lines revealed reduced gene expression of plant hormone signalling genes relevant to plant-aphid interactions, indicating this effector enhances susceptibility by suppressing plant defences in barley. Our data suggests that some aphid effectors specifically function when expressed in host species, and feature activities that benefit their corresponding aphid species.