bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human iPSC-based models highlight defective glial and neuronal differentiation from neural progenitor cells in metachromatic leukodystrophy
Authors: Frati Giacomo , Luciani Marco , Meneghini Vasco , De Cicco Silvia , Ståhlman Marcus , Blomqvist Maria , Grossi Serena , Filocamo Mirella , Morena Francesco , Menegon Andrea , Martino Sabata , Gritti Angela 
Published: June 2018

AbstractThe pathological cascade leading from primary storage to neural cell dysfunction and death in metachromatic leukodystrophy (MLD) has been poorly elucidated in human-derived neural cell systems. In the present study, we have modeled the progression of pathological events during the differentiation of patient-specific iPSCs to neuroepithelial progenitor cells (iPSC-NPCs) and mature neurons, astrocytes, and oligodendrocytes at the morphological, molecular, and biochemical level. We showed significant sulfatide accumulation and altered sulfatide composition during the differentiation of MLD iPSC-NPCs into neuronal and glial cells. Changes in sulfatide levels and composition were accompanied by the expansion of the lysosomal compartment, oxidative stress, and apoptosis. The neuronal and glial differentiation capacity of MLD iPSC-NPCs was significantly impaired. We showed delayed appearance and/or reduced levels of oligodendroglial and astroglial markers as well as reduced number of neurons and disorganized neuronal network. Restoration of a functional Arylsulfatase A (ARSA) enzyme in MLD cells using lentiviral-mediated gene transfer normalized sulfatide levels and composition, globally rescuing the pathological phenotype. Our study points to MLD iPSC-derived neural progeny as a useful in vitro model to assess the impact of ARSA deficiency along NPC differentiation into neurons and glial cells. In addition, iPSC-derived neural cultures allowed testing the impact of ARSA reconstitution/overexpression on disease correction and, importantly, on the biology and functional features of human NPCs, with important therapeutic implications.
Efficient and self-adaptive in-situ learning in multilayer memristor neural networks
Authors: Li Can , Belkin Daniel , Li Yunning , Yan Peng , Hu Miao , Ge Ning , Jiang Hao , Montgomery Eric , Lin Peng , Wang Zhongrui , Song Wenhao , Strachan John Paul , Barnell Mark , Wu Qing , Williams R. Stanley , Yang J. Joshua , Xia Qiangfei 
Published: June 2018

AbstractMemristors with tunable resistance states are emerging building blocks of artificial neural networks. However, in situ learning on a large-scale multiple-layer memristor network has yet to be demonstrated because of challenges in device property engineering and circuit integration. Here we monolithically integrate hafnium oxide-based memristors with a foundry-made transistor array into a multiple-layer neural network. We experimentally demonstrate in situ learning capability and achieve competitive classification accuracy on a standard machine learning dataset, which further confirms that the training algorithm allows the network to adapt to hardware imperfections. Our simulation using the experimental parameters suggests that a larger network would further increase the classification accuracy. The memristor neural network is a promising hardware platform for artificial intelligence with high speed-energy efficiency.
Patient derived organoids to model rare prostate cancer phenotypes
Authors: Puca Loredana , Bareja Rohan , Prandi Davide , Shaw Reid , Benelli Matteo , Karthaus Wouter R. , Hess Judy , Sigouros Michael , Donoghue Adam , Kossai Myriam , Gao Dong , Cyrta Joanna , Sailer Verena , Vosoughi Aram , Pauli Chantal , Churakova Yelena , Cheung Cynthia , Deonarine Lesa Dayal , McNary Terra J. , Rosati Rachele , Tagawa Scott T. , Nanus David M. , Mosquera Juan Miguel , Sawyers Charles L. , Chen Yu , Inghirami Giorgio , Rao Rema A. , Grandori Carla , Elemento Olivier , Sboner Andrea , Demichelis Francesca , Rubin Mark A. , Beltran Himisha 
Published: June 2018

AbstractA major hurdle in the study of rare tumors is a lack of existing preclinical models. Neuroendocrine prostate cancer is an uncommon and aggressive histologic variant of prostate cancer that may arise de novo or as a mechanism of treatment resistance in patients with pre-existing castration-resistant prostate cancer. There are few available models to study neuroendocrine prostate cancer. Here, we report the generation and characterization of tumor organoids derived from needle biopsies of metastatic lesions from four patients. We demonstrate genomic, transcriptomic, and epigenomic concordance between organoids and their corresponding patient tumors. We utilize these organoids to understand the biologic role of the epigenetic modifier EZH2 in driving molecular programs associated with neuroendocrine prostate cancer progression. High-throughput organoid drug screening nominated single agents and drug combinations suggesting repurposing opportunities. This proof of principle study represents a strategy for the study of rare cancer phenotypes.
Enhanced ocean-atmosphere carbon partitioning via the carbonate counter pump during the last deglacial
Authors: Duchamp-Alphonse Stéphanie , Siani Giuseppe , Michel Elisabeth , Beaufort Luc , Gally Yves , Jaccard Samuel L. 
Published: June 2018

AbstractSeveral synergistic mechanisms were likely involved in the last deglacial atmospheric pCO2 rise. Leading hypotheses invoke a release of deep-ocean carbon through enhanced convection in the Southern Ocean (SO) and concomitant decreased efficiency of the global soft-tissue pump (STP). However, the temporal evolution of both the STP and the carbonate counter pump (CCP) remains unclear, thus preventing the evaluation of their contributions to the pCO2 rise. Here we present sedimentary coccolith records combined with export production reconstructions from the Subantarctic Pacific to document the leverage the SO biological carbon pump (BCP) has imposed on deglacial pCO2. Our data suggest a weakening of BCP during the phases of carbon outgassing, due in part to an increased CCP along with higher surface ocean fertility and elevated [CO2aq]. We propose that reduced BCP efficiency combined with enhanced SO ventilation played a major role in propelling the Earth out of the last ice age.
ZOLA-3D allows flexible 3D localization microscopy over an adjustable axial range
Authors: Aristov Andrey , Lelandais Benoit , Rensen Elena , Zimmer Christophe 
Published: June 2018

AbstractSingle molecule localization microscopy can generate 3D super-resolution images without scanning by leveraging the axial variations of normal or engineered point spread functions (PSF). Successful implementation of these approaches for extended axial ranges remains, however, challenging. We present Zernike Optimized Localization Approach in 3D (ZOLA-3D), an easy-to-use computational and optical solution that achieves optimal resolution over a tunable axial range. We use ZOLA-3D to demonstrate 3D super-resolution imaging of mitochondria, nuclear pores and microtubules in entire nuclei or cells up to ~5 μm deep.
HEPATOKIN1 is a biochemistry-based model of liver metabolism for applications in medicine and pharmacology
Authors: Berndt Nikolaus , Bulik Sascha , Wallach Iwona , Wünsch Tilo , König Matthias , Stockmann Martin , Meierhofer David , Holzhütter Hermann-Georg 
Published: June 2018

AbstractThe epidemic increase of non-alcoholic fatty liver diseases (NAFLD) requires a deeper understanding of the regulatory circuits controlling the response of liver metabolism to nutritional challenges, medical drugs, and genetic enzyme variants. As in vivo studies of human liver metabolism are encumbered with serious ethical and technical issues, we developed a comprehensive biochemistry-based kinetic model of the central liver metabolism including the regulation of enzyme activities by their reactants, allosteric effectors, and hormone-dependent phosphorylation. The utility of the model for basic research and applications in medicine and pharmacology is illustrated by simulating diurnal variations of the metabolic state of the liver at various perturbations caused by nutritional challenges (alcohol), drugs (valproate), and inherited enzyme disorders (galactosemia). Using proteomics data to scale maximal enzyme activities, the model is used to highlight differences in the metabolic functions of normal hepatocytes and malignant liver cells (adenoma and hepatocellular carcinoma).
DNA methylation as a mediator of HLA-DRB1*15:01 and a protective variant in multiple sclerosis
Authors: Kular Lara , Liu Yun , Ruhrmann Sabrina , Zheleznyakova Galina , Marabita Francesco , Gomez-Cabrero David , James Tojo , Ewing Ewoud , Lindén Magdalena , Górnikiewicz Bartosz , Aeinehband Shahin , Stridh Pernilla , Link Jenny , Andlauer Till F. M. , Gasperi Christiane , Wiendl Heinz , Zipp Frauke , Gold Ralf , Tackenberg Björn , Weber Frank , Hemmer Bernhard , Strauch Konstantin , Heilmann-Heimbach Stefanie , Rawal Rajesh , Schminke Ulf , Schmidt Carsten O. , Kacprowski Tim , Franke Andre , Laudes Matthias , Dilthey Alexander T. , Celius Elisabeth G. , Søndergaard Helle B. , Tegnér Jesper , Harbo Hanne F. , Oturai Annette B. , Olafsson Sigurgeir , Eggertsson Hannes P. , Halldorsson Bjarni V. , Hjaltason Haukur , Olafsson Elias , Jonsdottir Ingileif , Stefansson Kari , Olsson Tomas , Piehl Fredrik , Ekström Tomas J. , Kockum Ingrid , Feinberg Andrew P. , Jagodic Maja 
Published: June 2018

AbstractThe human leukocyte antigen (HLA) haplotype DRB1*15:01 is the major risk factor for multiple sclerosis (MS). Here, we find that DRB1*15:01 is hypomethylated and predominantly expressed in monocytes among carriers of DRB1*15:01. A differentially methylated region (DMR) encompassing HLA-DRB1 exon 2 is particularly affected and displays methylation-sensitive regulatory properties in vitro. Causal inference and Mendelian randomization provide evidence that HLA variants mediate risk for MS via changes in the HLA-DRB1 DMR that modify HLA-DRB1 expression. Meta-analysis of 14,259 cases and 171,347 controls confirms that these variants confer risk from DRB1*15:01 and also identifies a protective variant (rs9267649, p < 3.32 × 10−8, odds ratio = 0.86) after conditioning for all MS-associated variants in the region. rs9267649 is associated with increased DNA methylation at the HLA-DRB1 DMR and reduced expression of HLA-DRB1, suggesting a modulation of the DRB1*15:01 effect. Our integrative approach provides insights into the molecular mechanisms of MS susceptibility and suggests putative therapeutic strategies targeting a methylation-mediated regulation of the major risk gene.
Nanoscale electrical conductivity imaging using a nitrogen-vacancy center in diamond
Authors: Ariyaratne Amila , Bluvstein Dolev , Myers Bryan A. , Jayich Ania C. Bleszynski 
Published: June 2018

AbstractThe electrical conductivity of a material can feature subtle, non-trivial, and spatially varying signatures with critical insight into the material’s underlying physics. Here we demonstrate a conductivity imaging technique based on the atom-sized nitrogen-vacancy (NV) defect in diamond that offers local, quantitative, and non-invasive conductivity imaging with nanoscale spatial resolution. We monitor the spin relaxation rate of a single NV center in a scanning probe geometry to quantitatively image the magnetic fluctuations produced by thermal electron motion in nanopatterned metallic conductors. We achieve 40-nm scale spatial resolution of the conductivity and realize a 25-fold increase in imaging speed by implementing spin-to-charge conversion readout of a shallow NV center. NV-based conductivity imaging can probe condensed-matter systems in a new regime not accessible to existing technologies, and as a model example, we project readily achievable imaging of nanoscale phase separation in complex oxides.
Author Correction: Meridional heat transport variability induced by mesoscale processes in the subpolar North Atlantic
Authors: Zhao Jian , Bower Amy , Yang Jiayan , Lin Xiaopei 
Published: June 2018

The original version of this Article omitted the author N. Penny Holliday from the National Oceanography Centre, European Way, Southampton SO14 3ZH, UK. Consequently, the following was originally omitted from the Acknowledgements: ‘N.P.H. and the JR302 cruise were funded through the UK Natural Environment Research Council programmes UK OSNAP (NE/K010875/1), RAGNARRoCC (NE/K002511/1) and the Extended Ellett Line (National Capability)’. The corrected version of the Acknowledgements also removes the following from the original version: ‘The Zonally Accumulated Heat Transport in observation was calculated by N.P.H. from the National Ocean Center, United Kingdom’.Additionally, the following was originally omitted from the Author Contributions: ‘N.P.H. calculated the observed Zonally Accumulated Heat Transport along the OSNAP east section’.This has been corrected in both the PDF and HTML versions of the Article.
Thermodynamic and structural anomalies of water nanodroplets
Authors: Malek Shahrazad M. A. , Poole Peter H. , Saika-Voivod Ivan 
Published: June 2018

AbstractLiquid water nanodroplets are important in earth’s climate, and are valuable for studying supercooled water because they resist crystallisation well below the bulk freezing temperature. Bulk liquid water has well-known thermodynamic anomalies, such as a density maximum, and when supercooled is hypothesised to exhibit a liquid–liquid phase transition (LLPT) at elevated pressure. However, it is not known how these bulk anomalies might manifest themselves in nanodroplets. Here we show, using simulations of the TIP4P/2005 water model, that bulk anomalies occur in nanodroplets as small as 360 molecules. We also show that the Laplace pressure inside small droplets reaches 220 MPa at 180 K, conditions close to the LLPT of TIP4P/2005. While the density and pressure inside nanodroplets coincide with bulk values at moderate supercooling, we show that deviations emerge at lower temperature, as well as significant radial density gradients, which arise from and signal the approach to the LLPT.
Neural mechanisms for selectively tuning in to the target speaker in a naturalistic noisy situation
Authors: Dai Bohan , Chen Chuansheng , Long Yuhang , Zheng Lifen , Zhao Hui , Bai Xialu , Liu Wenda , Zhang Yuxuan , Liu Li , Guo Taomei , Ding Guosheng , Lu Chunming 
Published: June 2018

AbstractThe neural mechanism for selectively tuning in to a target speaker while tuning out the others in a multi-speaker situation (i.e., the cocktail-party effect) remains elusive. Here we addressed this issue by measuring brain activity simultaneously from a listener and from multiple speakers while they were involved in naturalistic conversations. Results consistently show selectively enhanced interpersonal neural synchronization (INS) between the listener and the attended speaker at left temporal–parietal junction, compared with that between the listener and the unattended speaker across different multi-speaker situations. Moreover, INS increases significantly prior to the occurrence of verbal responses, and even when the listener’s brain activity precedes that of the speaker. The INS increase is independent of brain-to-speech synchronization in both the anatomical location and frequency range. These findings suggest that INS underlies the selective process in a multi-speaker situation through neural predictions at the content level but not the sensory level of speech.
Assembly of Gold Nanorods on HSA Amyloid Fibrils to Develop a Conductive Nanoscaffold for Potential Biomedical and Biosensing Applications
Authors: Taheri Ramezan Ali , Akhtari Yasin , Tohidi Moghadam Tahereh , Ranjbar Bijan 
Published: June 2018

AbstractToday, Gold Nanorods have promised variety of applications in conjugation with biomolecules of interest. Discovery of functional amyloids has also been highlighted with possible use in designing high performance materials. To exploit dual properties of both Nano and Bio counterparts in new functional materials, this effort has focused on synthesis of a potential hybrid system of Gold nanorods (GNRs) and HSA amyloid fibrils to develop a conductive nanoscaffold. UV-Vis spectroscopy, Thioflavin T (ThT) assay, Far-UV Circular Dichroism (CD) spectropolarimetry, fluorescence and Transmission Electron microscopy were used to characterize formation of the nanostructures and amyloid fibrils. Surface plasmon resonance of GNRs was also monitored upon interaction with HSA amyloid fibrils, showing that the plasmonic component of the hybrid system has maintained its characteristic rod morphology without any perturbations. Analysis of Nyquist plots for the hybrid nanoscaffold showed that the electronic behavior of the hybrid system has been enhanced due to the presence of the assembled GNRs. Results of this investigation highlight the possibility of fabricating hybrid nano-bioscaffolds as promising candidates in versatile biomedical and biosensing applications.
Bandgap Tunable AgInS based Quantum Dots for High Contrast Cell Imaging with Enhanced Photodynamic and Antifungal Applications
Authors: Mir Irshad Ahmad , Radhakrishanan V. S. , Rawat Kamla , Prasad Tulika , Bohidar H. B. 
Published: June 2018

AbstractHerein, we report a facile microwave-assisted synthesis of cadmium-free water-soluble silver indium sulfide (AgInS2 or AIS) and AgInS@ZnS (or AIS@ZnS) core-shell quantum dots (QDs) using glutathione (GSH) as stabilizer. The core and core-shell nanocrystals exhibit tunable bandgap ranging of 2.3–3.1 and 2.4–3.5 eV, mean particle size of 2.5 and 3.25 nm, quantum yield of 26% and 49%, and fluorescence lifetimes of 326 and 438 ns, respectively. The core-shell QDs exhibit color-tunable emission in the visible region (500 to 600 nm), where the tunability was achieved by varying the molar ratio of Ag:In in the precursors. In vitro evaluation of antifungal activity of these water/ buffer stable QDs against the fungal pathogen, Candida albicans demonstrated that these were not toxic to the fungal cells upto a concentration of 100 µg/ml for 16 hours of incubation. Confocal imaging and spectrofluorometric studies showed enhanced fluorescence inside the microbial cells suggesting that AIS@ZnS particles had the capability to easily penetrate the cells. The increased generation of reactive oxygen species was evaluated for the core-shell QDs (photosensitizers) by using 9, 10-anthracenediyl-bis(methylene)dimalonic acid (ABMDMA) as singlet oxygen (1O2) scavenger molecule. These QDs have the potential for use as high contrast cell imaging, photodynamic and antifungal agents.
Subtropical hibernation in juvenile tegu lizards (Salvator merianae): insights from intestine redox dynamics
Authors: Moreira Daniel C. , Welker Alexis F. , Campos Élida G. , de Souza Silvia Cristina R. , Hermes-Lima Marcelo 
Published: June 2018

AbstractJuvenile tegu lizards (Salvator merianae) experience gradual and mild temperature changes from autumn to winter in their habitat. This tropical/subtropical reptile enter a state of dormancy, with an 80% reduction in metabolic rate, that remains almost constant during winter. The redox metabolism in non-mammalian vertebrates that hibernate under such distinguished conditions is poorly understood. We analyzed the redox metabolism in the intestine of juvenile tegus during different stages of their first annual cycle. The effect of food deprivation (in spring) was also studied to compare with fasting during hibernation. Both winter dormancy and food deprivation caused decreases in reduced glutathione levels and glutathione transferase activity. While glutathione peroxidase and glutathione transferase activities decreased during winter dormancy, as well as glutathione (GSH) levels, other antioxidant enzymes (catalase, superoxide dismutase and glutathione reductase) remained unchanged. Notably, levels of disulfide glutathione (GSSG) were 2.1-fold higher in late autumn, when animals were in the process of depressing metabolism towards hibernation. This increased “oxidative tonus” could be due to a disruption in NADPH-dependent antioxidant systems. In dormancy, GSSG and lipid hydroperoxides were diminished by 60–70%. The results suggest that the entrance into hibernation is the main challenge for the redox homeostasis in the intestine of juvenile tegus.
The level of ROCK1 and ROCK2 in patients with pulmonary hypertension in plateau area
Authors: Liu Bing , Chang Rong , Duan Zhili , Zhang Xiaofei , Shen Yusong , Liu Xiangbo , Wu Jinchun , Tuo Yajun , Luo Junming 
Published: June 2018

AbstractPulmonary hypertension (PH) is defined as the mean pulmonary artery pressure (mPAP) ≥25 mmHg under the sea level in resting state. ROCK1 and ROCK2 can be combined to cause the damage of vascular endothelial function. To explore the differences of ROCK1 and ROCK2 in subjects with pulmonary hypertension or normal pulmonary artery pressure in plateau area, and to further understand the mechanism of Rho/rho-kinase pathway activation for promoting pulmonary hypertension, we collected 64 patients with pulmonary hypertension and 87 normal pulmonary artery healthy controls. All subjects were hospitalized in Cardiology or Respiration Department of Qinghai Provincial Peoples’ Hospital from December 2016 to June 2017. The pulmonary artery systolic pressure was measured by Doppler ultrasound, and serum ROCK1 and ROCK2 levels were tested by enzyme linked immunosorbent assay (ELISA). We found that the serum ROCK2 concentration in the pulmonary hypertension group was significantly higher than that in the control group, but serum ROCK1 level had no significant difference. ROCK2 plays a leading role in pulmonary hypertension in the plateau region, so selective ROCK2 inhibitors will be more effective in improving pulmonary hypertension.
Acute infarction after mechanical thrombectomy is better delineable in virtual non-contrast compared to conventional images using a dual-layer spectral CT
Authors: Riederer Isabelle , Fingerle Alexander A. , Baum Thomas , Kirschke Jan S. , Rummeny Ernst J. , Noël Peter B. , Pfeiffer Daniela 
Published: June 2018

AbstractThe aim was to evaluate Virtual Non-Contrast (VNC)-CT images for the detection of acute infarcts in the brain after mechanical thrombectomy using a dual-layer spectral CT. 29 patients between September 2016 and February 2017 with unenhanced head spectral-CT after mechanical thrombectomy and available follow-up images (MRI, n:26; CT, n:3) were included. VNC-CT and conventional CT (CT) images were reconstructed using dedicated software. Based on those, contrast-to-noise ratio (CNR), and the volume of infarction were measured semi-automatically in VNC-CT, CT and MRI. Furthermore, two readers independently assessed the VNC-CT and CT images in a randomized order by using the ASPECT score, and inter-rater reliability, sensitivity and specificity were calculated. CNR was significantly higher in VNC-CT compared to CT (3.1 ± 1.5 versus 1.1 ± 1.1, p < 0.001). The mean estimated volume of infarction was significantly higher in VNC-CT compared to CT (72% versus 55% of the volume measured in MRI, p < 0.005). Inter-rater reliability was higher in VNC-CT compared to CT (0.751 versus 0.625) and sensitivity was higher in VNC-CT compared to CT (73% versus 55%). In conclusion, acute ischemic lesions after mechanical thrombectomy are better definable in VNC-CT compared to CT images using a dual-layer spectral CT system.