bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differentiation therapy and the mechanisms that terminate cancer cell proliferation without harming normal cells
Authors: Enane Francis O. , Saunthararajah Yogen , Korc Murray 
Published: September 2018

AbstractChemotherapeutic drugs have a common intent to activate apoptosis in tumor cells. However, master regulators of apoptosis (e.g., p53, p16/CDKN2A) are frequently genetically inactivated in cancers, resulting in multidrug resistance. An alternative, p53-independent method for terminating malignant proliferation is to engage terminal-differentiation. Normally, the exponential proliferation of lineage-committed progenitors, coordinated by the master transcription factor (TF) MYC, is self-limited by forward-differentiation to terminal lineage-fates. In cancers, however, this exponential proliferation is disengaged from terminal-differentiation. The mechanisms underlying this decoupling are mostly unknown. We performed a systematic review of published literature (January 2007–June 2018) to identify gene pathways linked to differentiation-failure in three treatment-recalcitrant cancers: hepatocellular carcinoma (HCC), ovarian cancer (OVC), and pancreatic ductal adenocarcinoma (PDAC). We analyzed key gene alterations in various apoptosis, proliferation and differentiation pathways to determine whether it is possible to predict treatment outcomes and suggest novel therapies. Poorly differentiated tumors were linked to poorer survival across histologies. Our analyses suggested loss-of-function events to master TF drivers of lineage-fates and their cofactors as being linked to differentiation-failure: genomic data in TCGA and ICGC databases demonstrated frequent haploinsufficiency of lineage master TFs (e.g., GATA4/6) in poorly differentiated tumors; the coactivators that these TFs use to activate genes (e.g. ARID1A, PBRM1) were also frequently inactivated by genetic mutation and/or deletion. By contrast, corepressor components (e.g., DNMT1, EED, UHRF1, and BAZ1A/B), that oppose coactivators to repress or turn off genes, were frequently amplified instead, and the level of amplification was highest in poorly differentiated lesions. This selection by neoplastic evolution towards unbalanced activity of transcriptional corepressors suggests these enzymes as candidate targets for inhibition aiming to re-engage forward-differentiation. This notion is supported by both pre-clinical and clinical trial literature.
Neuronal heterogeneity and stereotyped connectivity in the auditory afferent system
Authors: Petitpré Charles , Wu Haohao , Sharma Anil , Tokarska Anna , Fontanet Paula , Wang Yiqiao , Helmbacher Françoise , Yackle Kevin , Silberberg Gilad , Hadjab Saida , Lallemend François 
Published: September 2018

AbstractSpiral ganglion (SG) neurons of the cochlea convey all auditory inputs to the brain, yet the cellular and molecular complexity necessary to decode the various acoustic features in the SG has remained unresolved. Using single-cell RNA sequencing, we identify four types of SG neurons, including three novel subclasses of type I neurons and the type II neurons, and provide a comprehensive genetic framework that define their potential synaptic communication patterns. The connectivity patterns of the three subclasses of type I neurons with inner hair cells and their electrophysiological profiles suggest that they represent the intensity-coding properties of auditory afferents. Moreover, neuron type specification is already established at birth, indicating a neuronal diversification process independent of neuronal activity. Thus, this work provides a transcriptional catalog of neuron types in the cochlea, which serves as a valuable resource for dissecting cell-type-specific functions of dedicated afferents in auditory perception and in hearing disorders.
Singlet oxygen imaging using fluorescent probe Singlet Oxygen Sensor Green in photosynthetic organisms
Authors: Prasad Ankush , Sedlářová Michaela , Pospíšil Pavel 
Published: September 2018

AbstractFormation of singlet oxygen (1O2) was reported to accompany light stress in plants, contributing to cell signaling or oxidative damage. So far, Singlet Oxygen Sensor Green (SOSG) has been the only commercialized fluorescent probe for 1O2 imaging though it suffers from several limitations (unequal penetration and photosensitization) that need to be carefully considered to avoid misinterpretation of the analysed data. Herein, we present results of a comprehensive study focused on the appropriateness of SOSG for 1O2 imaging in three model photosynthetic organisms, unicellular cyanobacteria Synechocystis sp. PCC 6803, unicellular green alga Chlamydomonas reinhardtii and higher plant Arabidopsis thaliana. Penetration of SOSG differs in both unicellular organisms; while it is rather convenient for Chlamydomonas it is restricted by the presence of mucoid sheath of Synechocystis, which penetrability might be improved by mild heating. In Arabidopsis, SOSG penetration is limited due to tissue complexity which can be increased by pressure infiltration using a shut syringe. Photosensitization of SOSG and SOSG endoperoxide formed by its interaction with 1O2 might be prevented by illumination of samples by a red light. When measured under controlled conditions given above, SOSG might serve as specific probe for detection of intracellular 1O2 formation in photosynthetic organisms.
Systems pharmacology-based exploration reveals mechanisms of anti-steatotic effects of Jiang Zhi Granule on non-alcoholic fatty liver disease
Authors: Zheng Yiyuan , Wang Miao , Zheng Peiyong , Tang Xudong , Ji Guang 
Published: September 2018

AbstractNon-alcoholic fatty liver disease (NAFLD), which is in parallel with the obesity epidemic, accounts for a large amount of all chronic liver disease. Jiang Zhi Granule (JZG), a clinically used herbal formula, is developed in accordance with traditional Chinese medicine (TCM) pathogenesis for treating patients with NAFLD. In previous studies, the anti-steatotic effects of JZG against NAFLD have been demonstrated, and in this study, a systems pharmacology approach was used to explore the pharmacological mechanisms of JZG by predicting the active compounds within the herbal formula and their corresponding therapeutic targets. Its therapeutic efficacy was confirmed in the beginning of this study, and JZG was shown to significantly improve hepatic dysfunction and lipid droplet accumulation in PA-treated hepatocytes. Systems pharmacology was then performed to identify the active compounds in as well as to predict the therapeutic targets of this Chinese herbal prescription. Enrichment analyses indicated that the mechanisms of the anti-steatotic effects of JZG against NAFLD might be associated with lipid droplet degradation via autophagy, and a series of in vitro and in vivo validation experiments was subsequently performed to confirm that JZG could activate autophagy though the mTOR signalling to improve NAFLD.
Comparison of frequency and strain-rate domain mechanical characterization
Authors: Bartolini Luca , Iannuzzi Davide , Mattei Giorgio 
Published: September 2018

AbstractIndentation is becoming increasingly popular to test soft tissues and (bio)materials. Each material exhibits an unknown intrinsic “mechanical behaviour”. However, limited consensus on its “mechanical properties” (i.e. quantitative descriptors of mechanical behaviour) is generally present in the literature due to a number of factors, which include sample preparation, testing method and analysis model chosen. Viscoelastic characterisation – critical in applications subjected to dynamic loading conditions – can be performed in either the time- or frequency-domain. It is thus important to selectively investigate whether the testing domain affects the mechanical results or not. We recently presented an optomechanical indentation tool which enables both strain-rate (nano-$$\dot{\varepsilon }M$$

ε
̇

M
) and frequency domain (DMA) measurements while keeping the sample under the same physical conditions and eliminating any other variability factor. In this study, a poly(dimethylsiloxane) sample was characterised with our system. The DMA data were inverted to the time-domain through integral transformations and then directly related to nano-$$\dot{\varepsilon }M$$

ε
̇

M
strain-rate dependent results, showing that, even though the data do not perfectly overlap, there is an excellent correlation between them. This approach indicates that one can convert an oscillatory measurement into a strain-rate one and still capture the trend of the “mechanical behaviour” of the sample investigated.
Implantable Photothermal Agents based on Gold Nanorods-Encapsulated Microcube
Authors: Moon Hyun June , Ku Minhee , Lee Hyunjee , Yoon Nara , Yang Jaemoon , Bong Ki Wan 
Published: September 2018

AbstractGold nanorods (GNRs) are of great interest in cancer therapy given their ability to ablate tumor cells using deep tissue-penetrating near-infrared light. GNRs coated with tumor-specific moieties have the potential to target tumor tissue to minimize damage to normal tissue. However, perfect targeting is difficult to achieve given that nanoparticles could be broadly dispersed inside the body. Moreover, interaction between targeting groups and biological molecules could lower targeting abilities, resulting in off-target accumulation which might produce nanotoxicity. Here we introduce GNR-encapsulated microcubes (GNR@MCs) that can be utilized as implantable photothermal agents. GNR@MCs are created by encapsulating GNRs in polymeric networks via stop flow lithography (SFL), a one-phase synthesis technique which allows for creation of surfactant-free, uniform particles, and injection of GNR@MCs into the body after a simple rinse step. GNRs are highly packed and firmly encapsulated inside MCs, and entrapped GNRs exhibit optical properties comparable to that of unbound GNRs and photothermal efficiency (58%) in line with that of nano-sized agents (51–95%). Photothermal ablation in murine models is achieved using GNR@MCs stably implanted into the tumor tissue, which suggests that GNR@MCs can be a safe and effective platform for cancer therapy.
In vitro studies on space-conforming self-assembling silk hydrogels as a mesenchymal stem cell-support matrix suitable for minimally invasive brain application
Authors: Osama I. , Gorenkova N. , McKittrick C. M. , Wongpinyochit T. , Goudie A. , Seib F. P. , Carswell H. V. O. 
Published: September 2018

AbstractAdvanced cell therapies require robust delivery materials and silk is a promising contender with a long clinical track record. Our aim was to optimise self-assembling silk hydrogels as a mesenchymal stem cell (MSC)-support matrix that would allow future minimally invasive brain application. We used sonication energy to programme the transition of silk (1–5% w/v) secondary structure from a random coil to a stable β-sheet configuration. This allowed fine tuning of self-assembling silk hydrogels to achieve space conformity in the absence of any silk hydrogel swelling and to support uniform cell distribution as well as cell viability. Embedded cells underwent significant proliferation over 14 days in vitro, with the best proliferation achieved with 2% w/v hydrogels. Embedded MSCs showed significantly better viability in vitro after injection through a 30G needle when the gels were in the pre-gelled versus post-gelled state. Silk hydrogels (4% w/v) with physical characteristics matching brain tissue were visualised in preliminary in vivo experiments to exhibit good space conformity in an ischemic cavity (intraluminal thread middle cerebral artery occlusion model) in adult male Sprague-Dawley rats (n = 3). This study informs on optimal MSC-hydrogel matrix conditions for minimally invasive application as a platform for future experiments targeting brain repair.
Objective Evaluation of Multiple Sclerosis Lesion Segmentation using a Data Management and Processing Infrastructure
Authors: Commowick Olivier , Istace Audrey , Kain Michaël , Laurent Baptiste , Leray Florent , Simon Mathieu , Pop Sorina Camarasu , Girard Pascal , Améli Roxana , Ferré Jean-Christophe , Kerbrat Anne , Tourdias Thomas , Cervenansky Frédéric , Glatard Tristan , Beaumont Jérémy , Doyle Senan , Forbes Florence , Knight Jesse , Khademi April , Mahbod Amirreza , Wang Chunliang , McKinley Richard , Wagner Franca , Muschelli John , Sweeney Elizabeth , Roura Eloy , Lladó Xavier , Santos Michel M. , Santos Wellington P. , Silva-Filho Abel G. , Tomas-Fernandez Xavier , Urien Hélène , Bloch Isabelle , Valverde Sergi , Cabezas Mariano , Vera-Olmos Francisco Javier , Malpica Norberto , Guttmann Charles , Vukusic Sandra , Edan Gilles , Dojat Michel , Styner Martin , Warfield Simon K. , Cotton François , Barillot Christian 
Published: September 2018

AbstractWe present a study of multiple sclerosis segmentation algorithms conducted at the international MICCAI 2016 challenge. This challenge was operated using a new open-science computing infrastructure. This allowed for the automatic and independent evaluation of a large range of algorithms in a fair and completely automatic manner. This computing infrastructure was used to evaluate thirteen methods of MS lesions segmentation, exploring a broad range of state-of-theart algorithms, against a high-quality database of 53 MS cases coming from four centers following a common definition of the acquisition protocol. Each case was annotated manually by an unprecedented number of seven different experts. Results of the challenge highlighted that automatic algorithms, including the recent machine learning methods (random forests, deep learning, …), are still trailing human expertise on both detection and delineation criteria. In addition, we demonstrate that computing a statistically robust consensus of the algorithms performs closer to human expertise on one score (segmentation) although still trailing on detection scores.
Surface Proximity Effect, Imprint Memory of Ferroelectric Twins, and Tweed in the Paraelectric Phase of BaTiO3
Authors: Mathieu C. , Lubin C. , Le Doueff G. , Cattelan M. , Gemeiner P. , Dkhil B. , Salje E. K. H. , Barrett N. 
Published: September 2018

AbstractWe have used energy-filtered photoemission electron microscopy (PEEM) at the photoemission threshold to carry out a microscopic scale characterization of the surface charge and domain structure of the (001) surface in BaTiO3. Signatures of ferroelectric and ferroelastic domains, and tweed, dominate the surface structure of BaTiO3at room temperature. The surface ferroic signatures are maintained on heating to temperature (~550 K), well above the transition temperature (393 K). This surface proximity effect provides the mechanism for memory of the bulk ferroelectric domain arrangement up to 150 K above TCand thus can be considered as a robust fingerprint of the ferroelectric state near the surface. Self-reversal of polarization is observed for the tweed below TCand for the surface domains above TC. Annealing at higher temperature triggers the dynamic tweed which in turn allows a full reorganization of the ferroic domain configuration.
Structural insights into antigen recognition of an anti-β-(1,6)-β-(1,3)-D-glucan antibody
Authors: Sung Kwang Hoon , Josewski Jörn , Dübel Stefan , Blankenfeldt Wulf , Rau Udo 
Published: September 2018

AbstractSchizophyllan (SCH) is a high molecular weight homopolysaccharide composed of a β-(1,3)-D-glucan main chain with branching β-(1,6)-bound D-glucose residues. It forms triple helices that are highly stable towards heat and extreme pH, which provides SCH with interesting properties for industrial and medical applications. The recombinant anti-SCH antibody JoJ48C11 recognizes SCH and related β-(1,6)-branched β-(1,3)-D-glucans, but details governing its specificity are not known. Here, we fill this gap by determining crystal structures of the antigen binding fragment (Fab) of JoJ48C11 in the apo form and in complex with the unbranched β-(1,3)-D-glucose hexamer laminarihexaose 3.0 and 2.4 Å resolution, respectively. Together with docking studies, this allowed construction of a JoJ48C11/triple-helical SCH complex, leading to the identification of eight amino acid residues of JoJ48C11 (Tyr27H, His35H, Trp47H, Trp100H, Asp105H; Asp49L, Lys52L, Trp90L) that contribute to the recognition of glucose units from all three chains of the SCH triple helix. The importance of these amino acids was confirmed by mutagenesis and ELISA-based analysis. Our work provides an explanation for the specific recognition of triple-helical β-(1,6)-branched β-(1,3)-D-glucans by JoJ48C11 and provides another structure example for anti-carbohydrate antibodies.
“Green” Aqueous Synthesis and Advanced Spectral Characterization of Size-Selected Cu2ZnSnS4 Nanocrystal Inks
Authors: Stroyuk Oleksandr , Raevskaya Alexandra , Selyshchev Oleksandr , Dzhagan Volodymyr , Gaponik Nikolai , Zahn Dietrich R. T. , Eychmüller Alexander 
Published: September 2018

AbstractStructure, composition, and optical properties of colloidal mercaptoacetate-stabilized Cu2ZnSnS4 (CZTS) nanocrystal inks produced by a “green” method directly in aqueous solutions were characterized. A size-selective precipitation procedure using 2-propanol as a non-solvent allows separating a series of fractions of CZTS nanocrystals with an average size (bandgap) varying from 3 nm (1.72 eV) to 2 nm (2.04 eV). The size-selected CZTS nanocrystals revealed also phonon confinement, with the main phonon mode frequency varying by about 4 cm−1 between 2 nm and 3 nm NCs.
Differential HDAC1/2 network analysis reveals a role for prefoldin/CCT in HDAC1/2 complex assembly
Authors: Banks Charles A. S. , Miah Sayem , Adams Mark K. , Eubanks Cassandra G. , Thornton Janet L. , Florens Laurence , Washburn Michael P. 
Published: September 2018

AbstractHDAC1 and HDAC2 are components of several corepressor complexes (NuRD, Sin3, CoREST and MiDAC) that regulate transcription by deacetylating histones resulting in a more compact chromatin environment. This limits access of transcriptional machinery to genes and silences transcription. While using an AP-MS approach to map HDAC1/2 protein interaction networks, we noticed that N-terminally tagged versions of HDAC1 and HDAC2 did not assemble into HDAC corepressor complexes as expected, but instead appeared to be stalled with components of the prefoldin-CCT chaperonin pathway. These N-terminally tagged HDACs were also catalytically inactive. In contrast to the N-terminally tagged HDACs, C-terminally tagged HDAC1 and HDAC2 captured complete histone deacetylase complexes and the purified proteins had deacetylation activity that could be inhibited by SAHA (Vorinostat), a Class I/II HDAC inhibitor. This tag-mediated reprogramming of the HDAC1/2 protein interaction network suggests a mechanism whereby HDAC1 is first loaded into the CCT complex by prefoldin to complete folding, and then assembled into active, functional HDAC complexes. Imaging revealed that the prefoldin subunit VBP1 colocalises with nuclear HDAC1, suggesting that delivery of HDAC1 to the CCT complex happens in the nucleus.
Mindful breath awareness meditation facilitates efficiency gains in brain networks: A steady-state visually evoked potentials study
Authors: Schöne Benjamin , Gruber Thomas , Graetz Sebastian , Bernhof Martin , Malinowski Peter 
Published: September 2018

AbstractThe beneficial effects of mindfulness-based therapeutic interventions have stimulated a rapidly growing body of scientific research into underlying psychological processes. Resulting evidence indicates that engaging with mindfulness meditation is associated with increased performance on a range of cognitive tasks. However, the mechanisms promoting these improvements require further investigation. We studied changes in behavioural performance of 34 participants during a multiple object tracking (MOT) task that taps core cognitive processes, namely sustained selective visual attention and spatial working memory. Concurrently, we recorded the steady-state visually evoked potential (SSVEP), an EEG signal elicited by the continuously flickering moving objects, and indicator of attentional engagement. Participants were tested before and after practicing eight weeks of mindful breath awareness meditation or progressive muscle relaxation as active control condition. The meditation group improved their MOT-performance and exhibited a reduction of SSVEP amplitudes, whereas no such changes were observed in the relaxation group. Neither group changed in self-reported positive affect and mindfulness, while a marginal increase in negative affect was observed in the mindfulness group. This novel way of combining MOT and SSVEP provides the important insight that mindful breath awareness meditation may lead to refinements of attention networks, enabling more efficient use of attentional resources.
Monolayer-graphene-based broadband and wide-angle perfect absorption structures in the near infrared
Authors: Fan Yansong , Guo Chucai , Zhu Zhihong , Xu Wei , Wu Fan , Yuan Xiaodong , Qin Shiqiao 
Published: September 2018

AbstractBroadband optical absorption structures in the near infrared by coupling monolayer-graphene with periodical metal structures are proposed and demonstrated numerically. Optical absorption of graphene with over-50%-absorption bandwidth up to hundreds of nanometer caused by magnetic dipole resonances and magnetic coupling effect are investigated in detail, and the demonstrated bandwidths are one order higher than those caused by dielectric guiding mode resonances. In addition, the influences of geometrical parameters of structures are fully analyzed and these demonstrated structures show angular-insensitive absorption for oblique incidence in a large angular range. The demonstrated absorption structures in this work provide new design ideas in the realization of advanced graphene-based optoelectronic devices.
Origin of relationship between ferromagnetic response and damage in stretched systems
Authors: Merabtine S. , Zighem F. , Garcia-Sanchez A. , Gunasekaran V. , Belmeguenai M. , Zhou X. , Lupo P. , Adeyeye A. O. , Faurie D. 
Published: September 2018

AbstractThis article presents a study whose purpose is to elucidate the damage effects in thin films on their magnetic response. Co40Fe40B20 and Ni80Fe20 films of different nanometric thicknesses were stretched by more than 10% and in situ probed by atomic force microscopy measurements to determine their irreversible mechanical behavior (multi-cracking, buckling). Once these phenomena have been well identified, magnetic behavior of these stretched systems has been studied by ferromagnetic resonance to measure resulting magnetic anisotropy and damping evolutions. All of these experimental studies show that the magnetic properties are mainly affected by the stresses generated during the damage but not by the local discontinuities induced by the numerous cracks and buckles. This is in particular confirmed by the almost zero sensitivity to the damage of the magnetic properties of Ni80Fe20 alloy which is known for its vanishing magnetostriction.