bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear FGFR2 negatively regulates hypoxia-induced cell invasion in prostate cancer by interacting with HIF-1 and HIF-2
Authors: Lee Jae Eun , Shin Seung-Hyun , Shin Hyun-Woo , Chun Yang-Sook , Park Jong-Wan 
Published: March 2019

AbstractThe fibroblast growth factor receptor 2 (FGFR2) is a membrane receptor that promotes cell proliferation and differentiation. FGFR2 is also present in the nucleus, which raises a question on a new role of FGFR2 in regulating gene expression. Hypoxia-inducible factors 1 and 2 (HIF-1 and HIF-2) are nuclear proteins that transactivate many genes essential for cancer survival and metastasis under hypoxic conditions. Here, we investigated if nuclear FGFR2 modulates the HIF-driven hypoxic response. Using the TCGA database, we found that FGFR2 downregulation is associated with poor prognosis in prostate cancer. A gene-set enrichment analysis showed that metastasis- and hypoxia-related genes are associated with a low expression of FGFR2 in prostate cancer. Thus, we tested the possibility that FGFR2 negatively regulates the hypoxia-triggered metastasis of prostate cancer. FGFR2 controls migration and invasion of prostate cancer cells under hypoxia by inhibiting the HIF-driven gene expression. FGFR2 and HIF proteins co-localize and associate in the nucleus under hypoxia. FGFR2 interacts with the transactivation domain of HIF-1α and blocks the recruitment of coactivator p300, resulting in repression of HIF target genes. Based on these results, we propose a novel function of FGFR2 as a metastasis suppressor by controlling HIF-mediated hypoxic responses.
Host Taxon Predictor - A Tool for Predicting Taxon of the Host of a Newly Discovered Virus
Authors: Gałan Wojciech , Bąk Maciej , Jakubowska Małgorzata 
Published: March 2019

AbstractRecent advances in metagenomics provided a valuable alternative to culture-based approaches for better sampling viral diversity. However, some of newly identified viruses lack sequence similarity to any of previously sequenced ones, and cannot be easily assigned to their hosts. Here we present a bioinformatic approach to this problem. We developed classifiers capable of distinguishing eukaryotic viruses from the phages achieving almost 95% prediction accuracy. The classifiers are wrapped in Host Taxon Predictor (HTP) software written in Python which is freely available at https://github.com/wojciech-galan/viruses_classifier. HTP’s performance was later demonstrated on a collection of newly identified viral genomes and genome fragments. In summary, HTP is a culture- and alignment-free approach for distinction between phages and eukaryotic viruses. We have also shown that it is possible to further extend our method to go up the evolutionary tree and predict whether a virus can infect narrower taxa.
Matrix-bound nanovesicles prevent ischemia-induced retinal ganglion cell axon degeneration and death and preserve visual function
Authors: van der Merwe Yolandi , Faust Anne E. , Sakalli Ecem T. , Westrick Caroline C. , Hussey George , Chan Kevin C. , Conner Ian P. , Fu Valeria L. N. , Badylak Stephen F. , Steketee Michael B. 
Published: March 2019

AbstractInjury to retinal ganglion cells (RGC), central nervous system neurons that relay visual information to the brain, often leads to RGC axon degeneration and permanently lost visual function. Herein this study shows matrix-bound nanovesicles (MBV), a distinct class of extracellular nanovesicle localized specifically to the extracellular matrix (ECM) of healthy tissues, can neuroprotect RGCs and preserve visual function after severe, intraocular pressure (IOP) induced ischemia in rat. Intravitreal MBV injections attenuated IOP-induced RGC axon degeneration and death, protected RGC axon connectivity to visual nuclei in the brain, and prevented loss in retinal function as shown by histology, anterograde axon tracing, manganese-enhanced magnetic resonance imaging, and electroretinography. In the optic nerve, MBV also prevented IOP-induced decreases in growth associated protein-43 and IOP-induced increases in glial fibrillary acidic protein. In vitro studies showed MBV suppressed pro-inflammatory signaling by activated microglia and astrocytes, stimulated RGC neurite growth, and neuroprotected RGCs from neurotoxic media conditioned by pro-inflammatory astrocytes. Thus, MBV can positively modulate distinct signaling pathways (e.g., inflammation, cell death, and axon growth) in diverse cell types. Since MBV are naturally derived, bioactive factors present in numerous FDA approved devices, MBV may be readily useful, not only experimentally, but also clinically as immunomodulatory, neuroprotective factors for treating trauma or disease in the retina as well as other CNS tissues.
High individual variability in the transcriptomic response of Mediterranean mussels to Vibrio reveals the involvement of myticins in tissue injury
Authors: Rey-Campos Magalí , Moreira Rebeca , Valenzuela-Muñoz Valentina , Gallardo-Escárate Cristian , Novoa Beatriz , Figueras Antonio 
Published: March 2019

AbstractMediterranean mussels (Mytilus galloprovincialis) are sessile filter feeders that live in close contact with numerous marine microorganisms. As all invertebrates, they lack an adaptive immune response and how these animals are able to respond to a bacterial infection and discriminate it from their normal microbiome is difficult to understand. In this work, we conducted Illumina sequencing of the transcriptome of individual mussels before and after being infected with Vibrio splendidus. The control mussels were injected with filtered seawater. We demonstrate that a great variability exists among individual transcriptomes and that each animal showed an exclusive repertoire of genes not shared with other individuals. The regulated genes in both the control and infected mussels were also analyzed and, unexpectedly, the sampling before the injection was considered a stress stimulus strong enough to trigger and modulate the response in hemocytes, promoting cell migration and proliferation. We found a clear response against the injection of filtered seawater, suggesting a reaction against a tissue injury in which the myticins, the most expressed antimicrobial peptides in mussel, appeared significantly up regulated. Functional experiments with flow cytometry confirmed the transcriptomic results since a significant alteration of hemocyte structures and a decrease in the number of hemocytes positive for myticin C were found only after a Vibrio infection and not observed when mussels were bled before, generating a tissue injury. Therefore, we report the involvement of myticins in the response to a danger signal such as a simple injection in the adductor muscle.
Regional perturbation of gene transcription is associated with intrachromosomal rearrangements and gene fusion transcripts in high grade ovarian cancer
Authors: Krzyzanowski Paul M. , Sircoulomb Fabrice , Yousif Fouad , Normand Josee , La Rose Jose , E. Francis Kyle , Suarez Fernando , Beck Tim , McPherson John D. , Stein Lincoln D. , Rottapel Robert K. 
Published: March 2019

AbstractGenomic rearrangements are a hallmark of cancer biology and progression, allowing cells to rapidly transform through alterations in regulatory structures, changes in expression patterns, reprogramming of signaling pathways, and creation of novel transcripts via gene fusion events. Though functional gene fusions encoding oncogenic proteins are the most dramatic outcomes of genomic rearrangements, we investigated the relationship between rearrangements evidenced by fusion transcripts and local expression changes in cancer using transcriptome data alone. 9,953 gene fusion predictions from 418 primary serious ovarian cancer tumors were analyzed, identifying depletions of gene fusion breakpoints within coding regions of fused genes as well as an N-terminal enrichment of breakpoints within fused genes. We identified 48 genes with significant fusion-associated upregulation and furthermore demonstrate that significant regional overexpression of intact genes in patient transcriptomes occurs within 1 megabase of 78 novel gene fusions that function as central markers of these regions. We reveal that cancer transcriptomes select for gene fusions that preserve protein and protein domain coding potential. The association of gene fusion transcripts with neighboring gene overexpression supports rearrangements as mechanism through which cancer cells remodel their transcriptomes and identifies a new way to utilize gene fusions as indicators of regional expression changes in diseased cells with only transcriptomic data.
Keratoconic eyes with stable corneal tomography could benefit more from custom intraocular lens design than normal eyes
Authors: Schröder Simon , Eppig Timo , Liu Weidi , Schrecker Jens , Langenbucher Achim 
Published: March 2019

AbstractWe investigated whether eyes with keratoconic corneal tomography pattern could benefit more from aberration correction with custom intraocular lenses (IOLs) than normal cataractous eyes despite the effect of misalignment on the correction of aberrations. Custom IOLs (cIOLs) were calculated for twelve normal and twelve keratoconic eyes using personalized numerical ray tracing models. The Stiles-Crawford weighted root-mean-square spot-size (wRMS) at the virtual fovea was evaluated for cIOLs and aberration-neutral IOLs (nIOLs) in a simulated clinical study with 500 virtual IOL implantations per eye and per IOL. IOL misalignment (decentration, tilt, rotation) and pupillary ectopia (4.5 mm iris aperture) were varied upon each virtual implantation. The nIOLs achieved average wRMS of 16.4 ± 4.3 μm for normal, and 92.7 ± 34.4 μm for keratoconic eyes (mean ± standard deviation). The cIOLs reduced the average wRMS to 10.3 ± 5.8 μm for normal, and 28.5 ± 18.6 μm for keratoconic eyes. The cIOLs produced smaller wRMS than nIOLs in most virtual implantations (86.7% for normal and 99.4% for keratoconic eyes). IOL misalignment resulted in larger wRMS variations in the keratoconus group than in the normal group. Custom freeform IOL-optics-design may become a promising option for the correction of advanced aberrations in eyes with non-progressive keratoconic corneal tomography pattern.
Experimental demonstration of broadband light trapping by exciting surface modes of an all-dielectric taper
Authors: Huang Tsung-Yu , Yen Ta-Jen 
Published: March 2019

AbstractWe design an all-dielectric taper and then excite its surface modes by illuminating a plane wave upon the taper to achieve broadband light trapping spanning from 20 to 100 GHz. Via Lewin’s theory, such excitation of surface modes could be analogous to “trapped rainbow”, i.e., activation of negative Goos-Hänchen effect within a negative refractive waveguide. To further reinforce this statement, the corresponding power flow distributions within the all-dielectric taper are recorded in finite-integration time domain simulation and suggest that a chromatic incident pulse is indeed trapped at different critical thicknesses of the taper, a character of the negative refractive waveguide. Finally, the transmittance is measured and compared to the simulated ones. The two followed the similar trend.
Early neuropathological and neurobehavioral consequences of preterm birth in a rabbit model
Authors: van der Merwe Johannes , van der Veeken Lennart , Ferraris Sebastiano , Gsell Willy , Himmelreich Uwe , Toelen Jaan , Ourselin Sebastien , Melbourne Andrew , Vercauteren Tom , Deprest Jan 
Published: March 2019

AbstractPreterm birth is the most significant problem in contemporary obstetrics accounting for 5–18% of worldwide deliveries. Encephalopathy of prematurity encompasses the multifaceted diffuse brain injury resulting from preterm birth. Current animal models exploring the underlying pathophysiology of encephalopathy of prematurity employ significant insults to generate gross central nervous system abnormalities. To date the exclusive effect of prematurity was only studied in a non-human primate model. Therefore, we aimed to develop a representative encephalopathy of prematurity small animal model only dependent on preterm birth. Time mated New-Zealand white rabbit does were either delivered on 28 (pre-term) or 31 (term) postconceptional days by caesarean section. Neonatal rabbits underwent neurobehavioral evaluation on 32 days post conception and then were transcardially perfuse fixed. Neuropathological assessments for neuron and oligodendrocyte quantification, astrogliosis, apoptosis and cellular proliferation were performed. Lastly,ex-vivohigh-resolution Magnetic Resonance Imaging was used to calculate T1 volumetric and Diffusion Tensor Imaging derived fractional anisotropy and mean diffusivity. Preterm birth was associated with a motoric (posture instability, abnormal gait and decreased locomotion) and partial sensory (less pain responsiveness and failing righting reflex) deficits that coincided with global lower neuron densities, less oligodendrocyte precursors, increased apoptosis and less proliferation. These region-specific histological changes corresponded with Magnetic Resonance Diffusion Tensor Imaging differences. The most significant differences were seen in the hippocampus, caudate nucleus and thalamus of the preterm rabbits. In conclusion this model of preterm birth, in the absence of any other contributory events, resulted in measurable neurobehavioral deficits with associated brain structural and Magnetic Resonance Diffusion Tensor Imaging findings.
Hierarchical supercrystalline nanocomposites through the self-assembly of organically-modified ceramic nanoparticles
Authors: Domènech Berta , Kampferbeck Michael , Larsson Emanuel , Krekeler Tobias , Bor Büsra , Giuntini Diletta , Blankenburg Malte , Ritter Martin , Müller Martin , Vossmeyer Tobias , Weller Horst , Schneider Gerold A. 
Published: March 2019

AbstractBiomaterials often display outstanding combinations of mechanical properties thanks to their hierarchical structuring, which occurs through a dynamically and biologically controlled growth and self-assembly of their main constituents, typically mineral and protein. However, it is still challenging to obtain this ordered multiscale structural organization in synthetic 3D-nanocomposite materials. Herein, we report a new bottom-up approach for the synthesis of macroscale hierarchical nanocomposite materials in a single step. By controlling the content of organic phase during the self-assembly of monodisperse organically-modified nanoparticles (iron oxide with oleyl phosphate), either purely supercrystalline or hierarchically structured supercrystalline nanocomposite materials are obtained. Beyond a critical concentration of organic phase, a hierarchical material is consistently formed. In such a hierarchical material, individual organically-modified ceramic nanoparticles (Level 0) self-assemble into supercrystals in face-centered cubic superlattices (Level 1), which in turn form granules of up to hundreds of micrometers (Level 2). These micrometric granules are the constituents of the final mm-sized material. This approach demonstrates that the local concentration of organic phase and nano-building blocks during self-assembly controls the final material’s microstructure, and thus enables the fine-tuning of inorganic-organic nanocomposites’ mechanical behavior, paving the way towards the design of novel high-performance structural materials.
Event-to-event intensification of the hydrologic cycle from 1.5 °C to a 2 °C warmer world
Authors: Madakumbura Gavin D. , Kim Hyungjun , Utsumi Nobuyuki , Shiogama Hideo , Fischer Erich M. , Seland Øyvind , Scinocca John F. , Mitchell Daniel M. , Hirabayashi Yukiko , Oki Taikan 
Published: March 2019

AbstractThe Paris agreement was adopted to hold the global average temperature increase to well below 2 °C and pursue efforts to limit it to 1.5 °C. Here, we investigate the event-to-event hydroclimatic intensity, where an event is a pair of adjacent wet and dry spells, under future warming scenarios. According to a set of targeted multi-model large ensemble experiments, event-wise intensification will significantly increase globally for an additional 0.5 °C warming beyond 1.5 °C. In high latitudinal regions of the North American continent and Eurasia, this intensification is likely to involve overwhelming increases in wet spell intensity. Western and Eastern North America will likely experience more intense wet spells with negligible changes of dry spells. For the Mediterranean region, enhancement of dry spells seems to be dominating compared to the decrease in wet spell strength, and this will lead to an overall event-wise intensification. Furthermore, the extreme intensification could be 10 times stronger than the mean intensification. The high damage potential of such drastic changes between flood and drought conditions poses a major challenge to adaptation, and the findings suggest that risks could be substantially reduced by achieving a 1.5 °C target.
On the resilience of magic number theory for conductance ratios of aromatic molecules
Authors: Ulčakar Lara , Rejec Tomaž , Kokalj Jure , Sangtarash Sara , Sadeghi Hatef , Ramšak Anton , Jefferson John H. , Lambert Colin J. 
Published: March 2019

AbstractIf simple guidelines could be established for understanding how quantum interference (QI) can be exploited to control the flow of electricity through single molecules, then new functional molecules, which exploit room-temperature QI could be rapidly identified and subsequently screened. Recently it was demonstrated that conductance ratios of molecules with aromatic cores, with different connectivities to electrodes, can be predicted using a simple and easy-to-use “magic number theory.” In contrast with counting rules and “curly-arrow” descriptions of destructive QI, magic number theory captures the many forms of constructive QI, which can occur in molecular cores. Here we address the question of how conductance ratios are affected by electron-electron interactions. We find that due to cancellations of opposing trends, when Coulomb interactions and screening due to electrodes are switched on, conductance ratios are rather resilient. Consequently, qualitative trends in conductance ratios of molecules with extended pi systems can be predicted using simple ‘non-interacting’ magic number tables, without the need for large-scale computations. On the other hand, for certain connectivities, deviations from non-interacting conductance ratios can be significant and therefore such connectivities are of interest for probing the interplay between Coulomb interactions, connectivity and QI in single-molecule electron transport.
Comparison of pattern electroretinograms of glaucoma patients with parafoveal scotoma versus peripheral nasal step
Authors: Jung Kyoung In , Jeon Sooji , Kim Yong Chan , Park Chan Kee 
Published: March 2019

AbstractRetinal ganglion cells are distributed disproportionately with retinal eccentricity. Pattern electroretinogram (PERG) stimuli resulted in reduced responses with more eccentric stimuli. Therefore, we investigated whether PERG amplitude is associated with the location of visual field (VF) defect in primary open-angle glaucoma. Data from Twenty-nine glaucoma patients with a parafoveal scotoma (PFS) within the central 10° of fixation, 23 glaucoma patients with a peripheral nasal step (PNS), and 27 normal control subjects were analyzed in this study. Electroretinograms (ERGs) were obtained using a commercial ERG stimulator (Neuro-ERG). The thickness of the ganglion cell-inner plexiform layer (GCIPL) was measured using spectral-domain optical coherence tomography. A lower N95 amplitude was observed in both PFS and PNS compared to the normal control (Both P < 0.001). The N95 amplitude of the PFS group was significantly lower than that of the PNS group (P = 0.034). Average GCIPL thickness correlated positively with N95 amplitude (r = 0.368, P = 0.002), but did not correlate significantly with global mean sensitivity (r = 0.228, P = 0.073) or mean deviation on 24-2 standard automated perimetry (r = 0.173, P = 0.176). In conclusion, parafoveal VF defects were associated with the lower PERG amplitude. Therefore, it is necessary to take into account the location of VF defects in evaluating PERGs of glaucoma patients.
The traumatic brain injury mitigation effects of a new viscoelastic add-on liner
Authors: Siegkas Petros , Sharp David J. , Ghajari Mazdak 
Published: March 2019

AbstractTraumatic brain injury (TBI) affects millions of people worldwide with significant personal and social consequences. New materials and methods offer opportunities for improving designs of TBI prevention systems, such as helmets. We combined empirical impact tests and computational modelling to test the effectiveness of new viscoelastic add-on components in decreasing biomechanical forces within the brain during helmeted head impacts. Motorcycle helmets with and without the viscoelastic components were fitted on a head/neck assembly and were tested under oblique impact to replicate realistic accident conditions. Translational and rotational accelerations were measured during the tests. The inclusion of components reduced peak accelerations, with a significant effect for frontal impacts and a marginal effect for side and rear impacts. The head accelerations were then applied on a computational model of TBI to predict strain and strain-rate across the brain. The presence of viscoelastic components in the helmet decreased strain and strain-rate for frontal impacts at low impact speeds. The effect was less pronounced for front impact at high speeds and for side and rear impacts. This work shows the potential of the viscoelastic add-on components as lightweight and cost-effective solutions for enhancing helmet protection and decreasing strain and strain-rate across the brain during head impacts.
Deformation Twinning in Polycrystalline Mg Microstructures at High Strain Rates at the Atomic Scales
Authors: Agarwal Garvit , Dongare Avinash M. 
Published: March 2019

AbstractLarge scale molecular dynamics (MD) simulations are carried out to investigate the twinning behavior as well as the atomic scale micromechanisms of growth of tension and compression twins in polycrystalline Mg microstructures at high strain rates. A new defect characterization algorithm (extended-common neighbor analysis (E-CNA)) is developed that allows for an efficient identification of various types of twins in HCP microstructures. Unlike other local orientation analysis methods, the E-CNA method allows for atomic scale characterization of the structure of different types of twin boundaries in HCP microstructures. The MD simulations suggest that the local orientation of individual grains with the loading axis plays a critical role in determining the ability of grains to nucleate either compression twins or tension twins. The twinning behavior is observed through nucleation of a pair of planar faults and lateral growth of the twins occurs through nucleation of steps along the planar faults. The kinetics of migration of steps that determine the rate of growth of twins are investigated at the atomic scales. The twin tip velocity computed at high strain rates compares well with the experimentally reported values in the literature.