bluuebunny/crossref_metadata_2025_split huggingface dataset:
A RAC-GEF network critical for early intestinal tumourigenesis
Authors: Pickering K. A. , Gilroy K. , Cassidy J. W. , Fey S. K. , Najumudeen A. K. , Zeiger L. B. , Vincent D. F. , Gay D. M. , Johansson J. , Fordham R. P. , Miller B. , Clark W. , Hedley A. , Unal E. B. , Kiel C. , McGhee E. , Machesky L. M. , Nixon C. , Johnsson A. E. , Bain M. , Strathdee D. , van Hoof S. R. , Medema J. P. , Anderson K. I. , Brachmann S. M. , Stucke V. M. , Malliri A. , Drysdale M. , Turner M. , Serrano L. , Myant K. , Campbell A. D. , Sansom O. J. 
Published: January 2021

AbstractRAC1 activity is critical for intestinal homeostasis, and is required for hyperproliferation driven by loss of the tumour suppressor geneApcin the murine intestine. To avoid the impact of direct targeting upon homeostasis, we reasoned that indirect targeting of RAC1 via RAC-GEFs might be effective. Transcriptional profiling ofApcdeficient intestinal tissue identifiedVav3andTiam1as key targets. Deletion of these indicated that while TIAM1 deficiency could suppressApc-driven hyperproliferation, it had no impact upon tumourigenesis, while VAV3 deficiency had no effect. Intriguingly, deletion of either gene resulted in upregulation ofVav2, with subsequent targeting of all three (Vav2−/−Vav3−/−Tiam1−/−), profoundly suppressing hyperproliferation, tumourigenesis and RAC1 activity, without impacting normal homeostasis. Critically, the observed RAC-GEF dependency was negated by oncogenic KRAS mutation. Together, these data demonstrate that while targeting RAC-GEF molecules may have therapeutic impact at early stages, this benefit may be lost in late stage disease.
Targeting USP47 overcomes tyrosine kinase inhibitor resistance and eradicates leukemia stem/progenitor cells in chronic myelogenous leukemia
Authors: Lei Hu , Xu Han-Zhang , Shan Hui-Zhuang , Liu Meng , Lu Ying , Fang Zhi-Xiao , Jin Jin , Jing Bo , Xiao Xin-Hua , Gao Shen-Meng , Gao Feng-Hou , Xia Li , Yang Li , Liu Li-Gen , Wang Wei-Wei , Liu Chuan-Xu , Tong Yin , Wu Yun-Zhao , Zheng Jun-Ke , Chen Guo-Qiang , Zhou Li , Wu Ying-Li 
Published: January 2021

AbstractIdentifying novel drug targets to overcome resistance to tyrosine kinase inhibitors (TKIs) and eradicating leukemia stem/progenitor cells are required for the treatment of chronic myelogenous leukemia (CML). Here, we show that ubiquitin-specific peptidase 47 (USP47) is a potential target to overcome TKI resistance. Functional analysis shows that USP47 knockdown represses proliferation of CML cells sensitive or resistant to imatinib in vitro and in vivo. The knockout of Usp47 significantly inhibits BCR-ABL and BCR-ABLT315I-induced CML in mice with the reduction of Lin−Sca1+c-Kit+ CML stem/progenitor cells. Mechanistic studies show that stabilizing Y-box binding protein 1 contributes to USP47-mediated DNA damage repair in CML cells. Inhibiting USP47 by P22077 exerts cytotoxicity to CML cells with or without TKI resistance in vitro and in vivo. Moreover, P22077 eliminates leukemia stem/progenitor cells in CML mice. Together, targeting USP47 is a promising strategy to overcome TKI resistance and eradicate leukemia stem/progenitor cells in CML.
Rapid parallel adaptation despite gene flow in silent crickets
Authors: Zhang Xiao , Rayner Jack G. , Blaxter Mark , Bailey Nathan W. 
Published: January 2021

AbstractGene flow is predicted to impede parallel adaptation via de novo mutation, because it can introduce pre-existing adaptive alleles from population to population. We test this using Hawaiian crickets (Teleogryllus oceanicus) in which ‘flatwing’ males that lack sound-producing wing structures recently arose and spread under selection from an acoustically-orienting parasitoid. Morphometric and genetic comparisons identify distinct flatwing phenotypes in populations on three islands, localized to different loci. Nevertheless, we detect strong, recent and ongoing gene flow among the populations. Using genome scans and gene expression analysis we find that parallel evolution of flatwing on different islands is associated with shared genomic hotspots of adaptation that contain the genedoublesex, but the form of selection differs among islands and corresponds to known flatwing demographics in the wild. We thus show how parallel adaptation can occur on contemporary timescales despite gene flow, indicating that it could be less constrained than previously appreciated.
Synthesis of bio-based methylcyclopentadiene via direct hydrodeoxygenation of 3-methylcyclopent-2-enone derived from cellulose
Authors: Liu Yanting , Wang Ran , Qi Haifeng , Liu Xiao Yan , Li Guangyi , Wang Aiqin , Wang Xiaodong , Cong Yu , Zhang Tao , Li Ning 
Published: January 2021

AbstractThe exploration of highly efficient processes to convert renewable biomass to fuels and value-added chemicals is stimulated by the energy and environment problems. Herein, we describe an innovative route for the production of methylcyclopentadiene (MCPD) with cellulose, involving the transformation of cellulose into 3-methylcyclopent-2-enone (MCP) and subsequent selective hydrodeoxygenation to MCPD over a zinc-molybdenum oxide catalyst. The excellent performance of the zinc-molybdenum oxide catalyst is attributed to the formation of ZnMoO3 species during the reduction of ZnMoO4. Experiments reveal that preferential interaction of ZnMoO3 sites with the C=O bond instead of C=C bond in vapor-phase hydrodeoxygenation of MCP leads to highly selective formations of MCPD (with a carbon yield of 70%).
Three-phase electric power driven electroluminescent devices
Authors: Ji Junpeng , Perepichka Igor F. , Bai Junwu , Hu Dan , Xu Xiuru , Liu Ming , Wang Tao , Zhao Changbin , Meng Hong , Huang Wei 
Published: January 2021

AbstractCurrent power supply networks across the world are mostly based on three-phase electrical systems as an efficient and economical way for generation, transmission and distribution of electricity. Now, many electrically driven devices are relying on direct current or single-phase alternating current power supply that complicates utilization of three-phase power supply by requiring additional elements and costly switching mechanisms in the circuits. For example, light-emitting devices, which are now widely used for displays, solid-state lighting etc. typically operate with direct current power sources, although single-phase alternating current driven light-emitting devices have also gained significant attention in the recent years. Yet, light-emitting devices directly driven by a three-phase electric power has never been reported before. Benefiting from our precious work on coplanar electrodes structured light-emitting devices, in this article we demonstrate proof of a concept that light-emitting components can be driven by three-phase electric power without utilizing intricate back-end circuits and can compose state detection sensors and pixel units in a single device inspiring from three primary colors. Here we report a three-phase electric power driven electroluminescent devices fabricated featuring of flexibility and multi-functions. The design consists of three coplanar electrodes with dielectric layer(s) and light emission layer(s) coated on a top of input electrodes. It does not require transparent electrodes for electrical input and the light emission occurs when the top light-emitting layers are connected through a polar bridge. We demonstrate some applications of our three-phase electric power driven electroluminescent devices to realize pixel units, interactive rewritable displays and optical-output sensors. Furthermore, we also demonstrate the applicability of three-phase electrical power source to drive organic light-emitting devices with red, green and blue-emitting pixels and have shown high luminance (up to 6601 cd/m2) and current efficiency (up to 16.2 cd/A) from fabricated three-phase organic light-emitting devices. This novel geometry and driving method for electroluminescent devices is scalable and can be utilized even in a wider range of other types of light-emitting devices and special units.
Nanoelectromechanical modulation of a strongly-coupled plasmonic dimer
Authors: Song Jung-Hwan , Raza Søren , van de Groep Jorik , Kang Ju-Hyung , Li Qitong , Kik Pieter G. , Brongersma Mark L. 
Published: January 2021

AbstractThe ability of two nearly-touching plasmonic nanoparticles to squeeze light into a nanometer gap has provided a myriad of fundamental insights into light–matter interaction. In this work, we construct a nanoelectromechanical system (NEMS) that capitalizes on the unique, singular behavior that arises at sub-nanometer particle-spacings to create an electro-optical modulator. Using in situ electron energy loss spectroscopy in a transmission electron microscope, we map the spectral and spatial changes in the plasmonic modes as they hybridize and evolve from a weak to a strong coupling regime. In the strongly-coupled regime, we observe a very large mechanical tunability (~250 meV/nm) of the bonding-dipole plasmon resonance of the dimer at ~1 nm gap spacing, right before detrimental quantum effects set in. We leverage our findings to realize a prototype NEMS light-intensity modulator operating at ~10 MHz and with a power consumption of only 4 fJ/bit.
Unified divergent strategy towards the total synthesis of the three sub-classes of hasubanan alkaloids
Authors: Li Guang , Wang Qian , Zhu Jieping 
Published: January 2021

AbstractElegant asymmetric synthesis of hasubanan alkaloids have been developed over the past decades. However, a divergent approach leading to all three sub-classes of this family of natural products remains unknown. We report herein the realization of such an endeavor by accomplishing enantioselective total syntheses of four representative members. The synthesis is characterized by catalytic enantioselective construction of the tricyclic compounds from which three different intramolecular C-N bond forming processes leading to three topologically different hasubanan alkaloids are developed. An aza-Michael addition is used for the construction of the aza-[4.4.3]-propellane structure of (-)-cepharamine, whereas an oxidation/double deprotection/intramolecular hemiaminal forming sequence is developed to forge the bridged 6/6/6/6 tetracycle of (-)-cepharatines A and C and a domino bromination/double deprotection/cyclization sequence allows the build-up of the 6/6/5/5 fused tetracyclic structure of (−)-sinoracutine.
Chain-like gold nanoparticle clusters for multimodal photoacoustic microscopy and optical coherence tomography enhanced molecular imaging
Authors: Nguyen Van Phuc , Qian Wei , Li Yanxiu , Liu Bing , Aaberg Michael , Henry Jessica , Zhang Wei , Wang Xueding , Paulus Yannis M. 
Published: January 2021

AbstractColloidal gold nanoparticles (GNPs) serve as promising contrast agents in photoacoustic (PA) imaging, yet their utility is limited due to their absorption peak in the visible window overlapping with that of hemoglobin. To overcome such limitation, this report describes an ultrapure chain-like gold nanoparticle (CGNP) clusters with a redshift peak wavelength at 650 nm. The synthesized CGNP show an excellent biocompatibility and photostability. These nanoparticles are conjugated with arginine-glycine-aspartic acid (RGD) peptides (CGNP clusters-RGD) and validated in 12 living rabbits to perform multimodal photoacoustic microscopy (PAM) and optical coherence tomography (OCT) for visualization of newly developed blood vessels in the sub-retinal pigment epithelium (RPE) space of the retina, named choroidal neovascularization (CNV). The PAM system can achieve a 3D PAM image via a raster scan of 256 × 256 pixels within a time duration of 65 s. Intravenous injection of CGNP clusters-RGD bound to CNV and resulted in up to a 17-fold increase in PAM signal and 176% increase in OCT signal. Histology indicates that CGNP clusters could disassemble, which may facilitate its clearance from the body.
Site-specific incorporation of citrulline into proteins in mammalian cells
Authors: Mondal Santanu , Wang Shu , Zheng Yunan , Sen Sudeshna , Chatterjee Abhishek , Thompson Paul R. 
Published: January 2021

AbstractCitrullination is a post-translational modification (PTM) of arginine that is crucial for several physiological processes, including gene regulation and neutrophil extracellular trap formation. Despite recent advances, studies of protein citrullination remain challenging due to the difficulty of accessing proteins homogeneously citrullinated at a specific site. Herein, we report a technology that enables the site-specific incorporation of citrulline (Cit) into proteins in mammalian cells. This approach exploits an engineered E. coli-derived leucyl tRNA synthetase-tRNA pair that incorporates a photocaged-citrulline (SM60) into proteins in response to a nonsense codon. Subsequently, SM60 is readily converted to Cit with light in vitro and in living cells. To demonstrate the utility of the method, we biochemically characterize the effect of incorporating Cit at two known autocitrullination sites in Protein Arginine Deiminase 4 (PAD4, R372 and R374) and show that the R372Cit and R374Cit mutants are 181- and 9-fold less active than the wild-type enzyme. This technology possesses the potential to decipher the biology of citrullination.
Functional THz emitters based on Pancharatnam-Berry phase nonlinear metasurfaces
Authors: McDonnell Cormac , Deng Junhong , Sideris Symeon , Ellenbogen Tal , Li Guixin 
Published: January 2021

AbstractRecent advances in the science and technology of THz waves show promise for a wide variety of important applications in material inspection, imaging, and biomedical science amongst others. However, this promise is impeded by the lack of sufficiently functional THz emitters. Here, we introduce broadband THz emitters based on Pancharatnam-Berry phase nonlinear metasurfaces, which exhibit unique optical functionalities. Using these new emitters, we experimentally demonstrate tunable linear polarization of broadband single cycle THz pulses, the splitting of spin states and THz frequencies in the spatial domain, and the generation of few-cycle pulses with temporal polarization dispersion. Finally, we apply the ability of spin control of THz waves to demonstrate circular dichroism spectroscopy of amino acids. Altogether, we achieve nanoscale and all-optical control over the phase and polarization states of the emitted THz waves.
Insights into SusCD-mediated glycan import by a prominent gut symbiont
Authors: Gray Declan A. , White Joshua B. R. , Oluwole Abraham O. , Rath Parthasarathi , Glenwright Amy J. , Mazur Adam , Zahn Michael , Baslé Arnaud , Morland Carl , Evans Sasha L. , Cartmell Alan , Robinson Carol V. , Hiller Sebastian , Ranson Neil A. , Bolam David N. , van den Berg Bert 
Published: January 2021

AbstractIn Bacteroidetes, one of the dominant phyla of the mammalian gut, active uptake of large nutrients across the outer membrane is mediated by SusCD protein complexes via a “pedal bin” transport mechanism. However, many features of SusCD function in glycan uptake remain unclear, including ligand binding, the role of the SusD lid and the size limit for substrate transport. Here we characterise the β2,6 fructo-oligosaccharide (FOS) importing SusCD from Bacteroides thetaiotaomicron (Bt1762-Bt1763) to shed light on SusCD function. Co-crystal structures reveal residues involved in glycan recognition and suggest that the large binding cavity can accommodate several substrate molecules, each up to ~2.5 kDa in size, a finding supported by native mass spectrometry and isothermal titration calorimetry. Mutational studies in vivo provide functional insights into the key structural features of the SusCD apparatus and cryo-EM of the intact dimeric SusCD complex reveals several distinct states of the transporter, directly visualising the dynamics of the pedal bin transport mechanism.
Global computational alignment of tumor and cell line transcriptional profiles
Authors: Warren Allison , Chen Yejia , Jones Andrew , Shibue Tsukasa , Hahn William C. , Boehm Jesse S. , Vazquez Francisca , Tsherniak Aviad , McFarland James M. 
Published: January 2021

AbstractCell lines are key tools for preclinical cancer research, but it remains unclear how well they represent patient tumor samples. Direct comparisons of tumor and cell line transcriptional profiles are complicated by several factors, including the variable presence of normal cells in tumor samples. We thus develop an unsupervised alignment method (Celligner) and apply it to integrate several large-scale cell line and tumor RNA-Seq datasets. Although our method aligns the majority of cell lines with tumor samples of the same cancer type, it also reveals large differences in tumor similarity across cell lines. Using this approach, we identify several hundred cell lines from diverse lineages that present a more mesenchymal and undifferentiated transcriptional state and that exhibit distinct chemical and genetic dependencies. Celligner could be used to guide the selection of cell lines that more closely resemble patient tumors and improve the clinical translation of insights gained from cell lines.
MOF-in-COF molecular sieving membrane for selective hydrogen separation
Authors: Fan Hongwei , Peng Manhua , Strauss Ina , Mundstock Alexander , Meng Hong , Caro Jürgen 
Published: January 2021

AbstractCovalent organic frameworks (COFs) are promising materials for advanced molecular-separation membranes, but their wide nanometer-sized pores prevent selective gas separation through molecular sieving. Herein, we propose a MOF-in-COF concept for the confined growth of metal-organic framework (MOFs) inside a supported COF layer to prepare MOF-in-COF membranes. These membranes feature a unique MOF-in-COF micro/nanopore network, presumably due to the formation of MOFs as a pearl string-like chain of unit cells in the 1D channel of 2D COFs. The MOF-in-COF membranes exhibit an excellent hydrogen permeance (>3000 GPU) together with a significant enhancement of separation selectivity of hydrogen over other gases. The superior separation performance for H2/CO2 and H2/CH4 surpasses the Robeson upper bounds, benefiting from the synergy combining precise size sieving and fast molecular transport through the MOF-in-COF channels. The synthesis of different combinations of MOFs and COFs in robust MOF-in-COF membranes demonstrates the versatility of our design strategy.
Interfacial jamming reinforced Pickering emulgel for arbitrary architected nanocomposite with connected nanomaterial matrix
Authors: Zhang Yuanyuan , Zhu Guangming , Dong Biqin , Wang Feng , Tang Jiaoning , Stadler Florian J. , Yang Guanghui , Hong Shuxian , Xing Feng 
Published: January 2021

AbstractThree-dimensional (3D) nanocomposite (NC) printing has emerged as a major approach to translate nanomaterial physical properties to 3D geometries. However, 3D printing of conventional NCs with polymer matrix lacks control over nanomaterial connection that facilitates maximizing nanomaterial advantages. Thus, a printable NC that features nanomaterials matrix necessitates development, nevertheless, faces a challenge in preparation because of the trade-off between viscosity and interfacial stability. Here, we develop viscoelastic Pickering emulgels as NC inks through jamming nanomaterials on interfaces and in continuous phase. Emulgel composed of multiphases allow a vast range of composition options and superior printability. The excellent attributes initiate NC with spatial control over geometrics and functions through 3D printing of graphene oxide/phase-change materials emulgel, for instance. This versatile approach provides the means for architecting NCs with nanomaterial continuous phase whose performance does not constrain the vast array of available nanomaterials and allows for arbitrary hybridization and patterns.
Structural multi-colour invisible inks with submicron 4D printing of shape memory polymers
Authors: Zhang Wang , Wang Hao , Wang Hongtao , Chan John You En , Liu Hailong , Zhang Biao , Zhang Yuan-Fang , Agarwal Komal , Yang Xiaolong , Ranganath Anupama Sargur , Low Hong Yee , Ge Qi , Yang Joel K. W. 
Published: January 2021

AbstractFour-dimensional (4D) printing of shape memory polymer (SMP) imparts time responsive properties to 3D structures. Here, we explore 4D printing of a SMP in the submicron length scale, extending its applications to nanophononics. We report a new SMP photoresist based on Vero Clear achieving print features at a resolution of ~300 nm half pitch using two-photon polymerization lithography (TPL). Prints consisting of grids with size-tunable multi-colours enabled the study of shape memory effects to achieve large visual shifts through nanoscale structure deformation. As the nanostructures are flattened, the colours and printed information become invisible. Remarkably, the shape memory effect recovers the original surface morphology of the nanostructures along with its structural colour within seconds of heating above its glass transition temperature. The high-resolution printing and excellent reversibility in both microtopography and optical properties promises a platform for temperature-sensitive labels, information hiding for anti-counterfeiting, and tunable photonic devices.
Early-life-trauma triggers interferon-β resistance and neurodegeneration in a multiple sclerosis model via downregulated β1-adrenergic signaling
Authors: Khaw Yee Ming , Majid Danish , Oh Sungjong , Kang Eunjoo , Inoue Makoto 
Published: January 2021

AbstractEnvironmental triggers have important functions in multiple sclerosis (MS) susceptibility, phenotype, and trajectory. Exposure to early life trauma (ELT) has been associated with higher relapse rates in MS patients; however, the underlying mechanisms are not well-defined. Here we show ELT induces mechanistic and phenotypical alterations during experimental autoimmune encephalitis (EAE). ELT sustains downregulation of immune cell adrenergic receptors, which can be attributed to chronic norepinephrine circulation. ELT-subjected mice exhibit interferon-β resistance and neurodegeneration driven by lymphotoxin and CXCR2 involvement. These phenotypic changes are observed in control EAE mice treated with β1 adrenergic receptor antagonist. Conversely, β1 adrenergic receptor agonist treatment to ELT mice abrogates phenotype changes via restoration of immune cell β1 adrenergic receptor function. Our results indicate that ELT alters EAE phenotype via downregulation of β1 adrenergic signaling in immune cells. These results have implications for the effect of environmental factors in provoking disease heterogeneity and might enable prediction of long-term outcomes in MS.
Experimental validation of a modeling framework for upconversion enhancement in 1D-photonic crystals
Authors: Hofmann Clarissa L. M. , Fischer Stefan , Eriksen Emil H. , Bläsi Benedikt , Reitz Christian , Yazicioglu Deniz , Howard Ian A. , Richards Bryce S. , Goldschmidt Jan Christoph 
Published: January 2021

AbstractPhotonic structures can be designed to tailor luminescence properties of materials, which becomes particularly interesting for non-linear phenomena, such as photon upconversion. However, there is no adequate theoretical framework to optimize photonic structure designs for upconversion enhancement. Here, we present a comprehensive theoretical model describing photonic effects on upconversion and confirm the model’s predictions by experimental realization of 1D-photonic upconverter devices with large statistics and parameter scans. The measured upconversion photoluminescence enhancement reaches 82 ± 24% of the simulated enhancement, in the mean of 2480 separate measurements, scanning the irradiance and the excitation wavelength on 40 different sample designs. Additionally, the trends expected from the modeled interaction of photonic energy density enhancement, local density of optical states and internal upconversion dynamics, are clearly validated in all experimentally performed parameter scans. Our simulation tool now opens the possibility of precisely designing photonic structure designs for various upconverting materials and applications.