bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiation-induced bystander and abscopal effects: important lessons from preclinical models
Authors: Daguenet Elisabeth , Louati Safa , Wozny Anne-Sophie , Vial Nicolas , Gras Mathilde , Guy Jean-Baptiste , Vallard Alexis , Rodriguez-Lafrasse Claire , Magné Nicolas 
Published: June 2020

AbstractRadiotherapy is a pivotal component in the curative treatment of patients with localised cancer and isolated metastasis, as well as being used as a palliative strategy for patients with disseminated disease. The clinical efficacy of radiotherapy has traditionally been attributed to the local effects of ionising radiation, which induces cell death by directly and indirectly inducing DNA damage, but substantial work has uncovered an unexpected and dual relationship between tumour irradiation and the host immune system. In clinical practice, it is, therefore, tempting to tailor immunotherapies with radiotherapy in order to synergise innate and adaptive immunity against cancer cells, as well as to bypass immune tolerance and exhaustion, with the aim of facilitating tumour regression. However, our understanding of how radiation impacts on immune system activation is still in its early stages, and concerns and challenges regarding therapeutic applications still need to be overcome. With the increasing use of immunotherapy and its common combination with ionising radiation, this review briefly delineates current knowledge about the non-targeted effects of radiotherapy, and aims to provide insights, at the preclinical level, into the mechanisms that are involved with the potential to yield clinically relevant combinatorial approaches of radiotherapy and immunotherapy.
Targeting the ERG oncogene with splice-switching oligonucleotides as a novel therapeutic strategy in prostate cancer
Authors: Li Ling , Hobson Lisa , Perry Laura , Clark Bethany , Heavey Susan , Haider Aiman , Sridhar Ashwin , Shaw Greg , Kelly John , Freeman Alex , Wilson Ian , Whitaker Hayley , Nurmemmedov Elmar , Oltean Sebastian , Porazinski Sean , Ladomery Michael 
Published: June 2020

Abstract
Background
The ERG oncogene, a member of the ETS family of transcription factor encoding genes, is a genetic driver of prostate cancer. It is activated through a fusion with the androgen-responsive TMPRSS2 promoter in 50% of cases. There is therefore significant interest in developing novel therapeutic agents that target ERG. We have taken an antisense approach and designed morpholino-based oligonucleotides that target ERG by inducing skipping of its constitutive exon 4.

Methods
We designed antisense morpholino oligonucleotides (splice-switching oligonucleotides, SSOs) that target both the 5′ and 3′ splice sites of ERG’s exon 4. We tested their efficacy in terms of inducing exon 4 skipping in two ERG-positive cell lines, VCaP prostate cancer cells and MG63 osteosarcoma cells. We measured their effect on cell proliferation, migration and apoptosis. We also tested their effect on xenograft tumour growth in mice and on ERG protein expression in a human prostate cancer radical prostatectomy sample ex vivo.

Results
In VCaP cells, both SSOs were effective at inducing exon 4 skipping, which resulted in a reduction of overall ERG protein levels up to 96 h following a single transfection. SSO-induced ERG reduction decreased cell proliferation, cell migration and significantly increased apoptosis. We observed a concomitant reduction in protein levels for cyclin D1, c-Myc and the Wnt signalling pathway member β-catenin as well as a marker of activated Wnt signalling, p-LRP6. We tested the 3′ splice site SSO in MG63 xenografts in mice and observed a reduction in tumour growth. We also demonstrated that the 3′ splice site SSO caused a reduction in ERG expression in a patient-derived prostate tumour tissue cultured ex vivo.

Conclusions
We have successfully designed and tested morpholino-based SSOs that cause a marked reduction in ERG expression, resulting in decreased cell proliferation, a reduced migratory phenotype and increased apoptosis. Our initial tests on mouse xenografts and a human prostate cancer radical prostatectomy specimen indicate that SSOs can be effective for oncogene targeting in vivo. As such, this study encourages further in vivo therapeutic studies using SSOs targeting the ERG oncogene.
Human GBP1 binds LPS to initiate assembly of a caspase-4 activating platform on cytosolic bacteria
Authors: Santos José Carlos , Boucher Dave , Schneider Larisa Kapinos , Demarco Benjamin , Dilucca Marisa , Shkarina Kateryna , Heilig Rosalie , Chen Kaiwen W. , Lim Roderick Y. H. , Broz Petr 
Published: June 2020

AbstractThe human non-canonical inflammasome controls caspase-4 activation and gasdermin-D-dependent pyroptosis in response to cytosolic bacterial lipopolysaccharide (LPS). Since LPS binds and oligomerizes caspase-4, the pathway is thought to proceed without dedicated LPS sensors or an activation platform. Here we report that interferon-induced guanylate-binding proteins (GBPs) are required for non-canonical inflammasome activation by cytosolicSalmonellaor upon cytosolic delivery of LPS. GBP1 associates with the surface of cytosolicSalmonellaseconds after bacterial escape from their vacuole, initiating the recruitment of GBP2-4 to assemble a GBP coat. The GBP coat then promotes the recruitment of caspase-4 to the bacterial surface and caspase activation, in absence of bacteriolysis. Mechanistically, GBP1 binds LPS with high affinity through electrostatic interactions. Our findings indicate that in human epithelial cells GBP1 acts as a cytosolic LPS sensor and assembles a platform for caspase-4 recruitment and activation at LPS-containing membranes as the first step of non-canonical inflammasome signaling.
Quantifying microscale drivers for fatigue failure via coupled synchrotron X-ray characterization and simulations
Authors: Gustafson Sven , Ludwig Wolfgang , Shade Paul , Naragani Diwakar , Pagan Darren , Cook Phil , Yildirim Can , Detlefs Carsten , Sangid Michael D. 
Published: June 2020

AbstractDuring cyclic loading, localization of intragranular deformation due to crystallographic slip acts as a precursor for crack initiation, often at coherent twin boundaries. A suite of high-resolution synchrotron X-ray characterizations, coupled with a crystal plasticity simulation, was conducted on a polycrystalline nickel-based superalloy microstructure near a parent-twin boundary in order to understand the deformation localization behavior of this critical, 3D microstructural configuration. Dark-field X-ray microscopy was spatially linked to high energy X-ray diffraction microscopy and X-ray diffraction contrast tomography in order to quantify, with cutting-edge resolution, an intragranular misorientation and high elastic strain gradients near a twin boundary. These observations quantify the extreme sub-grain scale stress gradients present in polycrystalline microstructures, which often lead to fatigue failure.
The role of mPFC and MTL neurons in human choice under goal-conflict
Authors: Gazit Tomer , Gonen Tal , Gurevitch Guy , Cohen Noa , Strauss Ido , Zeevi Yoav , Yamin Hagar , Fahoum Firas , Hendler Talma , Fried Itzhak 
Published: June 2020

AbstractResolving approach-avoidance conflicts relies on encoding motivation outcomes and learning from past experiences. Accumulating evidence points to the role of the Medial Temporal Lobe (MTL) and Medial Prefrontal Cortex (mPFC) in these processes, but their differential contributions have not been convincingly deciphered in humans. We detect 310 neurons from mPFC and MTL from patients with epilepsy undergoing intracranial recordings and participating in a goal-conflict task where rewards and punishments could be controlled or not. mPFC neurons are more selective to punishments than rewards when controlled. However, only MTL firing following punishment is linked to a lower probability for subsequent approach behavior. mPFC response to punishment precedes a similar MTL response and affects subsequent behavior via an interaction with MTL firing. We thus propose a model where approach-avoidance conflict resolution in humans depends on outcome value tagging in mPFC neurons influencing encoding of such value in MTL to affect subsequent choice.
Synergism between IL7R and CXCR4 drives BCR-ABL induced transformation in Philadelphia chromosome-positive acute lymphoblastic leukemia
Authors: Abdelrasoul Hend , Vadakumchery Anila , Werner Markus , Lenk Lennart , Khadour Ahmad , Young Marc , El Ayoubi Omar , Vogiatzi Fotini , Krämer Markus , Schmid Vera , Chen Zhengshan , Yousafzai Yasar , Cario Gunnar , Schrappe Martin , Müschen Markus , Halsey Christina , Mulaw Medhanie A. , Schewe Denis M. , Hobeika Elias , Alsadeq Ameera , Jumaa Hassan 
Published: June 2020

AbstractPh+ acute lymphoblastic leukemia (ALL) is characterized by the expression of an oncogenic fusion kinase termed BCR-ABL1. Here, we show that interleukin 7 receptor (IL7R) interacts with the chemokine receptor CXCR4 to recruit BCR-ABL1 and JAK kinases in close proximity. Treatment with BCR-ABL1 kinase inhibitors results in elevated expression of IL7R which enables the survival of transformed cells when IL7 was added together with the kinase inhibitors. Importantly, treatment with anti-IL7R antibodies prevents leukemia development in xenotransplantation models using patient-derived Ph+ ALL cells. Our results suggest that the association between IL7R and CXCR4 serves as molecular platform for BCR-ABL1-induced transformation and development of Ph+ ALL. Targeting this platform with anti-IL7R antibody eliminates Ph+ ALL cells including those with resistance to commonly used ABL1 kinase inhibitors. Thus, anti-IL7R antibodies may provide alternative treatment options for ALL in general and may suppress incurable drug-resistant leukemia forms.
Large magnetoelectric coupling in multiferroic oxide heterostructures assembled via epitaxial lift-off
Authors: Pesquera D. , Khestanova E. , Ghidini M. , Zhang S. , Rooney A. P. , Maccherozzi F. , Riego P. , Farokhipoor S. , Kim J. , Moya X. , Vickers M. E. , Stelmashenko N. A. , Haigh S. J. , Dhesi S. S. , Mathur N. D. 
Published: June 2020

AbstractEpitaxial films may be released from growth substrates and transferred to structurally and chemically incompatible substrates, but epitaxial films of transition metal perovskite oxides have not been transferred to electroactive substrates for voltage control of their myriad functional properties. Here we demonstrate good strain transmission at the incoherent interface between a strain-released film of epitaxially grown ferromagnetic La0.7Sr0.3MnO3 and an electroactive substrate of ferroelectric 0.68Pb(Mg1/3Nb2/3)O3-0.32PbTiO3 in a different crystallographic orientation. Our strain-mediated magnetoelectric coupling compares well with respect to epitaxial heterostructures, where the epitaxy responsible for strong coupling can degrade film magnetization via strain and dislocations. Moreover, the electrical switching of magnetic anisotropy is repeatable and non-volatile. High-resolution magnetic vector maps reveal that micromagnetic behaviour is governed by electrically controlled strain and cracks in the film. Our demonstration should inspire others to control the physical/chemical properties in strain-released epitaxial oxide films by using electroactive substrates to impart strain via non-epitaxial interfaces.
Reconstruction of evolving nanostructures in ultrathin films with X-ray waveguide fluorescence holography
Authors: Jiang Zhang , Strzalka Joseph W. , Walko Donald A. , Wang Jin 
Published: June 2020

AbstractControlled synthesis of nanostructure ultrathin films is critical for applications in nanoelectronics, photonics, and energy generation and storage. The paucity of structural probes that are sensitive to nanometer-thick films and also capable of in-operando conditions with high spatiotemporal resolutions limits the understanding of morphology and dynamics in ultrathin films. Similar to X-ray fluorescence holography for crystals, where holograms are formed through the interference between the reference and the object waves, we demonstrated that an ultrathin film, being an X-ray waveguide, can also generate fluorescence holograms as a result of the establishment of X-ray standing waves. Coupled with model-independent reconstruction algorithms based on rigorous dynamical scattering theories, the thin-film-based X-ray waveguide fluorescence holography becomes a unique in situ and time-resolved imaging probe capable of elucidating the real-time nanostructure kinetics with unprecedented resolutions. Combined with chemical sensitive spectroscopic analysis, the reconstruction can yield element-specific morphology of embedding nanostructures in ultrathin films.
Economic use of plants is key to their naturalization success
Authors: van Kleunen Mark , Xu Xinyi , Yang Qiang , Maurel Noëlie , Zhang Zhijie , Dawson Wayne , Essl Franz , Kreft Holger , Pergl Jan , Pyšek Petr , Weigelt Patrick , Moser Dietmar , Lenzner Bernd , Fristoe Trevor S. 
Published: June 2020

AbstractHumans cultivate thousands of economic plants (i.e. plants with economic value) outside their native ranges. To analyze how this contributes to naturalization success, we combine global databases on economic uses and naturalization success of the world’s seed plants. Here we show that naturalization likelihood is 18 times higher for economic than non-economic plants. Naturalization success is highest for plants grown as animal food or for environmental uses (e.g. ornamentals), and increases with number of uses. Taxa from the Northern Hemisphere are disproportionately over-represented among economic plants, and economic plants from Asia have the greatest naturalization success. In regional naturalized floras, the percentage of economic plants exceeds the global percentage and increases towards the equator. Phylogenetic patterns in the naturalized flora partly result from phylogenetic patterns in the plants we cultivate. Our study illustrates that accounting for the intentional introduction of economic plants is key to unravelling drivers of plant naturalization.
Connecting glass-forming ability of binary mixtures of soft particles to equilibrium melting temperatures
Authors: Nie Yunhuan , Liu Jun , Guo Jialing , Xu Ning 
Published: June 2020

AbstractThe glass-forming ability is an important material property for manufacturing glasses and understanding the long-standing glass transition problem. Because of the nonequilibrium nature, it is difficult to develop the theory for it. Here we report that the glass-forming ability of binary mixtures of soft particles is related to the equilibrium melting temperatures. Due to the distinction in particle size or stiffness, the two components in a mixture effectively feel different melting temperatures, leading to a melting temperature gap. By varying the particle size, stiffness, and composition over a wide range of pressures, we establish a comprehensive picture for the glass-forming ability, based on our finding of the direct link between the glass-forming ability and the melting temperature gap. Our study reveals and explains the pressure and interaction dependence of the glass-forming ability of model glass-formers, and suggests strategies to optimize the glass-forming ability via the manipulation of particle interactions.
Lithium-ion electrolytic substrates for sub-1V high-performance transition metal dichalcogenide transistors and amplifiers
Authors: Alam Md Hasibul , Xu Zifan , Chowdhury Sayema , Jiang Zhanzhi , Taneja Deepyanti , Banerjee Sanjay K. , Lai Keji , Braga Maria Helena , Akinwande Deji 
Published: June 2020

AbstractElectrostatic gating of two-dimensional (2D) materials with ionic liquids (ILs), leading to the accumulation of high surface charge carrier densities, has been often exploited in 2D devices. However, the intrinsic liquid nature of ILs, their sensitivity to humidity, and the stress induced in frozen liquids inhibit ILs from constituting an ideal platform for electrostatic gating. Here we report a lithium-ion solid electrolyte substrate, demonstrating its application in high-performance back-gated n-type MoS2 and p-type WSe2 transistors with sub-threshold values approaching the ideal limit of 60 mV/dec and complementary inverter amplifier gain of 34, the highest among comparable amplifiers. Remarkably, these outstanding values were obtained under 1 V power supply. Microscopic studies of the transistor channel using microwave impedance microscopy reveal a homogeneous channel formation, indicative of a smooth interface between the TMD and underlying electrolytic substrate. These results establish lithium-ion substrates as a promising alternative to ILs for advanced thin-film devices.
Tuning reactivity of Fischer–Tropsch synthesis by regulating TiOx overlayer over Ru/TiO2 nanocatalysts
Authors: Zhang Yaru , Yang Xiaoli , Yang Xiaofeng , Duan Hongmin , Qi Haifeng , Su Yang , Liang Binglian , Tao Huabing , Liu Bin , Chen De , Su Xiong , Huang Yanqiang , Zhang Tao 
Published: June 2020

AbstractThe activity of Fischer–Tropsch synthesis (FTS) on metal-based nanocatalysts can be greatly promoted by the support of reducible oxides, while the role of support remains elusive. Herein, by varying the reduction condition to regulate the TiOx overlayer on Ru nanocatalysts, the reactivity of Ru/TiO2 nanocatalysts can be differentially modulated. The activity in FTS shows a volcano-like trend with increasing reduction temperature from 200 to 600 °C. Such a variation of activity is characterized to be related to the activation of CO on the TiOx overlayer at Ru/TiO2 interfaces. Further theoretical calculations suggest that the formation of reduced TiOx occurs facilely on the Ru surface, and it involves in the catalytic mechanism of FTS to facilitate the CO bond cleavage kinetically. This study provides a deep insight on the mechanism of TiOx overlayer in FTS, and offers an effective approach to tuning catalytic reactivity of metal nanocatalysts on reducible oxides.
Long lived second mode internal solitary waves in the Andaman Sea
Authors: Magalhaes J. M. , da Silva J. C. B. , Buijsman M. C. 
Published: June 2020

AbstractInternal waves are density oscillations propagating along the ocean’s inner stratification, which are now acknowledged as a key constituent of the ocean’s dynamics. They usually result from barotropic tides, which flow over bottom topography, causing density oscillations to propagate along the pycnocline with a tidal frequency (i.e. internal tides). These large-scale waves propagate away from their forcing bathymetry and frequently disintegrate into nonlinear short-scale (higher-frequency) internal wave packets. Typically, short-scale internal wave observations in the ocean are associated with vertical structures (in the water column) of the lowest fundamental mode. Higher vertical modes have recently been documented as well, but these are commonly short-lived (up to a few hours). However, unprecedented satellite images showing long-lived short-scale mode-2 internal waves have now been documented in the Andaman Sea, and we report here the companion results of a non-hydrostatic and fully nonlinear numerical model. The simulations reproduce the waves’ main characteristics as observed in satellite imagery, and the results suggest a resonant coupling with a larger-scale mode-4 internal tide as an explanation for their long-lived character.
In-situ characterization of ultrathin nickel silicides using 3D medium-energy ion scattering
Authors: Tran Tuan Thien , Jablonka Lukas , Lavoie Christian , Zhang Zhen , Primetzhofer Daniel 
Published: June 2020

AbstractEpitaxial ultrathin films are of utmost importance for state-of-the-art nanoelectronic devices, such as MOSFET transistors and non-volatile memories. At the same time, as the film thickness is reduced to a few nanometers, characterization of the materials is becoming challenging for commonly used methods. In this report, we demonstrate an approach for in-situ characterization of phase transitions of ultrathin nickel silicides using 3D medium-energy ion scattering. The technique provides simultaneously depth-resolved composition and real-space crystallography of the silicide films using a single sample and with a non-invasive probe. We show, for 10 nm Ni films on Si, that their composition follows a normal transition sequence, such as Ni-Ni2Si-NiSi. However, the transition process is significantly different for samples with initial Ni thickness of 3 nm. Depth-resolved crystallography shows that the Ni films transform from an as-deposited disordered layer to an epitaxial silicide layer at the temperature of ~290 °C, significantly lower than previously reported. The high depth resolution of the technique permits us to determine the composition of the ultrathin films to be 38% Ni and 62% Si.
Interferon-Dependent and Respiratory Virus-Specific Interference in Dual Infections of Airway Epithelia
Authors: Essaidi-Laziosi Manel , Geiser Johan , Huang Song , Constant Samuel , Kaiser Laurent , Tapparel Caroline 
Published: June 2020

AbstractMany respiratory viruses cocirculate in the population and multiple infections are commonly reported. The clinical impact of coinfection is unclear and may vary depending on the viral couples involved. Using three-dimensional reconstituted human airway epithelia and clinical viral strains, we investigated the interaction between influenza virus (Flu), respiratory syncytial virus (RSV) and rhinovirus (RV). We showed that Flu and RSV interfere with RV replication, whereas RV does not interfere with either of these viruses. We then experimentally demonstrated that, when present, the interference is not related to a block of viral entry but rather to type I and type III interferon (IFN), the front-line antiviral defense of the respiratory mucosa. Consistent with this observation, we highlighted the differential sensitivity of each virus to IFNs, with RV being the only virus significantly inhibited by IFN-λ and the most sensitive to IFN-α. Finally, as type III IFN is of therapeutic interest due to its low proinflammatory profile, we also assessed and confirmed an inhibitory effect of IFN-λ in the context of persistent RV infections. The present work provides mechanistic clues concerning innate immunity involvement during respiratory virus interactions and confirms that IFN-λ is a promising candidate in the treatment of RV infections.
Robust detection of undifferentiated iPSC among differentiated cells
Authors: Sekine Keisuke , Tsuzuki Syusaku , Yasui Ryota , Kobayashi Tatsuya , Ikeda Kazuki , Hamada Yuki , Kanai Eriko , Camp J. Gray , Treutlein Barbara , Ueno Yasuharu , Okamoto Satoshi , Taniguchi Hideki 
Published: June 2020

AbstractRecent progress in human induced pluripotent stem cells (iPSC) technologies suggest that iPSC application in regenerative medicine is a closer reality. Numerous challenges prevent iPSC application in the development of numerous tissues and for the treatment of various diseases. A key concern in therapeutic applications is the safety of the cell products to be transplanted into patients. Here, we present novel method for detecting residual undifferentiated iPSCs amongst directed differentiated cells of all three germ lineages. Marker genes, which are expressed specifically and highly in undifferentiated iPSC, were selected from single cell RNA sequence data to perform robust and sensitive detection of residual undifferentiated cells in differentiated cell products. ESRG (Embryonic Stem Cell Related), CNMD (Chondromodulin), and SFRP2 (Secreted Frizzled Related Protein 2) were well-correlated with the actual amounts of residual undifferentiated cells and could be used to detect residual cells in a highly sensitive manner using qPCR. In addition, such markers could be used to detect residual undifferentiated cells from various differentiated cells, including hepatic cells and pancreatic cells for the endodermal lineage, endothelial cells and mesenchymal cells for the mesodermal lineage, and neural cells for the ectodermal lineage. Our method facilitates robust validation and could enhance the safety of the cell products through the exclusion of undifferentiated iPSC.