bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dedifferentiation process driven by radiotherapy-induced HMGB1/TLR2/YAP/HIF-1α signaling enhances pancreatic cancer stemness
Authors: Zhang Lirong , Shi Hui , Chen Hongbo , Gong Aihua , Liu Yanfang , Song Lian , Xu Xuewen , You Tao , Fan Xin , Wang Dongqing , Cheng Fang , Zhu Haitao 
Published: September 2019

AbstractDifferentiated cancer cells reacquiring stem cell traits following radiotherapy may enrich cancer stem cells and accelerate tumor recurrence and metastasis. We are interested in the mechanistic role of dying cells-derived HMGB1 in CD133− pancreatic cancer cells dedifferentiation following radiotherapy. We firstly confirmed that X-ray irradiation induced differentiation of CD133− pancreatic cancer cells, from either sorted from patient samples or established cell lines, into cancer stem-like cells (iCSCs). Using an in vitro coculture model, X-ray irradiation induced dying cells to release HMGB1, which further promoted CD133− pancreatic cancer cells regaining stem cell traits, such as higher sphere forming ability and expressed higher level of stemness-related genes and proteins. Inhibiting the expression and activity of HMGB1 attenuated the dedifferentiation stimulating effect of irradiated, dying cells on C133− pancreatic cancer cells in vitro and in PDX models. Mechanistically, HMGB1 binding with TLR2 receptor functions in a paracrine manner to affect CD133− pancreatic cancer cells dedifferentiation via activating Hippo-YAP pathway and HIF-1α expression in oxygen independent manner in vitro and in vivo. We conclude that X-ray irradiation induces CD133− pancreatic cancer cell dedifferentiation into a CSC phenotype, and inhibiting HMGB1 may be a strategy to prevent CSC enrichment and further pancreatic carcinoma relapse.
Mechanically controlled reversible photoluminescence response in all-inorganic flexible transparent ferroelectric/mica heterostructures
Authors: Zheng Ming , Sun Hailing , Kwok K. W. 
Published: September 2019

AbstractThe ability to reversibly control the luminescent properties of functional materials with diverse external stimuli, such as an electric field, strain, and temperature, is crucial for designing high-performance optical devices. Here, we demonstrate that a purely mechanical strain in a flexible mica substrate triggered by bending can be used to dramatically modify the photoluminescence response of a Pr-doped Ba0.85Ca0.15Ti0.9Zr0.1O3epitaxial thin film in a stable and repeatable manner with a large gauge factor of up to 6853. The strong dependence of the photoluminescence performance on the mechanical bending arises from strain-induced variations in the lattice symmetry of the host film and the local crystal field around the Pr3+. In particular, because of the nature of mica, the film structure exhibits excellent antifatigue characteristics after 104bending cycles as well as high optical transparency in the range of 450–780 nm. This study provides a viable route for exploring the correlation between structural symmetry and photoluminescence in ferroelectric thin-film systems and offers new possibilities for developing all-inorganic, reconfigurable, transparent and flexible light sources, photodetectors, and wearable sensors.
Soybean antiviral immunity conferred by dsRNase targets the viral replication complex
Authors: Ishibashi Kazuhiro , Saruta Masayasu , Shimizu Takehiko , Shu Miao , Anai Toyoaki , Komatsu Kunihiko , Yamada Naohiro , Katayose Yuichi , Ishikawa Masayuki , Ishimoto Masao , Kaga Akito 
Published: September 2019

AbstractEukaryotic positive-strand RNA viruses replicate their genomes in membranous compartments formed in a host cell, which sequesters the dsRNA replication intermediate from antiviral immune surveillance. Here, we find that soybean has developed a way to overcome this sequestration. We report the positional cloning of the broad-spectrum soybean mosaic virus resistance gene Rsv4, which encodes an RNase H family protein with dsRNA-degrading activity. An active-site mutant of Rsv4 is incapable of inhibiting virus multiplication and is associated with an active viral RNA polymerase complex in infected cells. These results suggest that Rsv4 enters the viral replication compartment and degrades viral dsRNA. Inspired by this model, we design three plant-gene-derived dsRNases that can inhibit the multiplication of the respective target viruses. These findings suggest a method for developing crops resistant to any target positive-strand RNA virus by fusion of endogenous host genes.
Human immunoglobulin G hinge regulates agonistic anti-CD40 immunostimulatory and antitumour activities through biophysical flexibility
Authors: Liu Xiaobo , Zhao Yingjie , Shi Huan , Zhang Yan , Yin Xueying , Liu Mingdong , Zhang Huihui , He Yongning , Lu Boxun , Jin Tengchuan , Li Fubin 
Published: September 2019

AbstractHuman immunoglobulin G (IgG) agonistic antibodies targeting costimulatory immunoreceptors represent promising cancer immunotherapies yet to be developed. Whether, and how, human IgG hinge and Fc impact on their agonistic functions have been disputed. Here, we show that different natural human IgGs confer divergent agonistic anti-CD40 immunostimulatory and antitumour activities in FcγR-humanized mice, including inactive IgG3 and superior IgG2. This divergence is primarily due to their CH1-hinges despite all human IgGs requiring Fc-FcγR binding for optimal agonistic activities. Unexpectedly, biophysical flexibility of these CH1-hinges inversely correlates with, and can modulate, their agonistic potency. Furthermore, IgG Fcs optimized for selective FcγR binding synergize with and still require IgG hinge, selected for rigidity, to confer improved anti-CD40 immunostimulatory and antitumour activities. These findings highlight the importance of both hinge rigidity and selective FcγR binding in antibody agonistic function, and the need for newer strategies to modulate antibody agonism for improved clinical application.
Piezophototronic gated optofluidic logic computations empowering intrinsic reconfigurable switches
Authors: Purusothaman Yuvasree , Alluri Nagamalleswara Rao , Chandrasekhar Arunkumar , Venkateswaran Vivekananthan , Kim Sang-Jae 
Published: September 2019

AbstractOptofluidic nano/microsystems have advanced the realization of Boolean circuits, with drastic progression to achieve extensive scale integration of desirable optoelectronics to investigate multiple logic switches. In this context, we demonstrate the optofluidic logic operations with interfacial piezophototronic effect to promote multiple operations of electronic analogues. We report an optofluidic Y-channeled logic device with tunable metal-semiconductor-metal interfaces through mechanically induced strain elements. We investigate the configuration of an OR gate in a semiconductor-piezoelectric zinc oxide nanorod-manipulated optofluidic sensor, and its direct reconfiguration to logic AND through compressive strain-induced (−1%) piezoelectric negative polarizations. The exhibited strategy in optofluidic systems implemented with piezophototronic concept enables direct-on chip working of OR and AND logic with switchable photocurrent under identical analyte. Featured smart intrinsic switching between the Boolean optoelectronic gates (OR↔AND) ultimately reduces the need for cascaded logic circuits to operate multiple logic switches on-a-chip.
Ideological differences in the expanse of the moral circle
Authors: Waytz Adam , Iyer Ravi , Young Liane , Haidt Jonathan , Graham Jesse 
Published: September 2019

AbstractDo clashes between ideologies reflect policy differences or something more fundamental? The present research suggests they reflect core psychological differences such that liberals express compassion toward less structured and more encompassing entities (i.e., universalism), whereas conservatives express compassion toward more well-defined and less encompassing entities (i.e., parochialism). Here we report seven studies illustrating universalist versus parochial differences in compassion. Studies 1a-1c show that liberals, relative to conservatives, express greater moral concern toward friends relative to family, and the world relative to the nation. Studies 2a-2b demonstrate these universalist versus parochial preferences extend toward simple shapes depicted as proxies for loose versus tight social circles. Using stimuli devoid of political relevance demonstrates that the universalist-parochialist distinction does not simply reflect differing policy preferences. Studies 3a-3b indicate these universalist versus parochial tendencies extend to humans versus nonhumans more generally, demonstrating the breadth of these psychological differences.
Optical control of protein phosphatase function
Authors: Courtney Taylor M. , Deiters Alexander 
Published: September 2019

AbstractProtein phosphatases are involved in embryonic development, metabolic homeostasis, stress response, cell cycle transitions, and many other essential biological mechanisms. Unlike kinases, protein phosphatases remain understudied and less characterized. Traditional genetic and biochemical methods have contributed significantly to our understanding; however, these methodologies lack precise and acute spatiotemporal control. Here, we report the development of a light-activated protein phosphatase, the dual specificity phosphatase 6 (DUSP6 or MKP3). Through genetic code expansion, MKP3 is placed under optical control via two different approaches: (i) incorporation of a caged cysteine into the active site for controlling catalytic activity and (ii) incorporation of a caged lysine into the kinase interaction motif for controlling the protein-protein interaction between the phosphatase and its substrate. Both strategies are expected to be applicable to the engineering of a wide range of light-activated phosphatases. Applying the optogenetically controlled MKP3 in conjunction with live cell reporters, we discover that ERK nuclear translocation is regulated in a graded manner in response to increasing MKP3 activity.
Heisenberg-limited single-mode quantum metrology in a superconducting circuit
Authors: Wang W. , Wu Y. , Ma Y. , Cai W. , Hu L. , Mu X. , Xu Y. , Chen Zi-Jie , Wang H. , Song Y. P. , Yuan H. , Zou C.-L. , Duan L.-M. , Sun L. 
Published: September 2019

AbstractTwo-mode interferometers lay the foundations for quantum metrology. Instead of exploring quantum entanglement in the two-mode interferometers, a single bosonic mode also promises a measurement precision beyond the shot-noise limit (SNL) by taking advantage of the infinite-dimensional Hilbert space of Fock states. Here, we demonstrate a single-mode phase estimation that approaches the Heisenberg limit (HL) unconditionally. Due to the strong dispersive nonlinearity and long coherence time of a microwave cavity, quantum states of the form $$\left( {\left| 0 \right\rangle + \left| N \right\rangle } \right)/\sqrt 2$$

0

+

N

∕

2

can be generated, manipulated and detected with high fidelities, leading to an experimental phase estimation precision scaling as ∼N−0.94. A 9.1 dB enhancement of the precision over the SNL at N = 12 is achieved, which is only 1.7 dB away from the HL. Our experimental architecture is hardware efficient and can be combined with quantum error correction techniques to fight against decoherence, and thus promises quantum-enhanced sensing in practical applications.
Urothelial organoids originating from Cd49fhigh mouse stem cells display Notch-dependent differentiation capacity
Authors: Santos Catarina P. , Lapi Eleonora , Martínez de Villarreal Jaime , Álvaro-Espinosa Laura , Fernández-Barral Asunción , Barbáchano Antonio , Domínguez Orlando , Laughney Ashley M. , Megías Diego , Muñoz Alberto , Real Francisco X. 
Published: September 2019

AbstractUnderstanding urothelial stem cell biology and differentiation has been limited by the lack of methods for their unlimited propagation. Here, we establish mouse urothelial organoids that can be maintained uninterruptedly for >1 year. Organoid growth is dependent on EGF and Wnt activators. High CD49f/ITGA6 expression features a subpopulation of organoid-forming cells expressing basal markers. Upon differentiation, multilayered organoids undergo reduced proliferation, decreased cell layer number, urothelial program activation, and acquisition of barrier function. Pharmacological modulation of PPARγ and EGFR promotes differentiation. RNA sequencing highlighted genesets enriched in proliferative organoids (i.e. ribosome) and transcriptional networks involved in differentiation, including expression of Wnt ligands and Notch components. Single-cell RNA sequencing (scRNA-Seq) analysis of the organoids revealed five clusters with distinct gene expression profiles. Together with the use of γ-secretase inhibitors, scRNA-Seq confirms that Notch signaling is required for differentiation. Urothelial organoids provide a powerful tool to study cell regeneration and differentiation.
Boosting selective nitrogen reduction to ammonia on electron-deficient copper nanoparticles
Authors: Lin Yun-Xiao , Zhang Shi-Nan , Xue Zhong-Hua , Zhang Jun-Jun , Su Hui , Zhao Tian-Jian , Zhai Guang-Yao , Li Xin-Hao , Antonietti Markus , Chen Jie-Sheng 
Published: September 2019

AbstractProduction of ammonia is currently realized by the Haber–Bosch process, while electrochemical N2 fixation under ambient conditions is recognized as a promising green substitution in the near future. A lack of efficient electrocatalysts remains the primary hurdle for the initiation of potential electrocatalytic synthesis of ammonia. For cheaper metals, such as copper, limited progress has been made to date. In this work, we boost the N2 reduction reaction catalytic activity of Cu nanoparticles, which originally exhibited negligible N2 reduction reaction activity, via a local electron depletion effect. The electron-deficient Cu nanoparticles are brought in a Schottky rectifying contact with a polyimide support which retards the hydrogen evolution reaction process in basic electrolytes and facilitates the electrochemical N2 reduction reaction process under ambient aqueous conditions. This strategy of inducing electron deficiency provides new insight into the rational design of inexpensive N2 reduction reaction catalysts with high selectivity and activity.
A ‘parameiosis’ drives depolyploidization and homologous recombination in Candida albicans
Authors: Anderson Matthew Z. , Thomson Gregory J. , Hirakawa Matthew P. , Bennett Richard J. 
Published: September 2019

AbstractMeiosis is a conserved tenet of sexual reproduction in eukaryotes, yet this program is seemingly absent from many extant species. In the human fungal pathogen Candida albicans, mating of diploid cells generates tetraploid products that return to the diploid state via a non-meiotic process of depolyploidization known as concerted chromosome loss (CCL). Here, we report that recombination rates are more than three orders of magnitude higher during CCL than during normal mitotic growth. Furthermore, two conserved ‘meiosis-specific’ factors play central roles in CCL as SPO11 mediates DNA double-strand break formation while both SPO11 and REC8 regulate chromosome stability and promote inter-homolog recombination. Unexpectedly, SPO11 also promotes DNA repair and recombination during normal mitotic divisions. These results indicate that C. albicans CCL represents a ‘parameiosis’ that blurs the conventional boundaries between mitosis and meiosis. They also reveal parallels with depolyploidization in mammalian cells and provide potential insights into the evolution of meiosis.
Connective tissue fibroblasts from highly regenerative mammals are refractory to ROS-induced cellular senescence
Authors: Saxena Sandeep , Vekaria Hemendra , Sullivan Patrick G. , Seifert Ashley W. 
Published: September 2019

AbstractA surveillance system in mammals constantly monitors cell activity to protect against aberrant proliferation in response to damage, injury and oncogenic stress. Here we isolate and culture connective tissue fibroblasts from highly regenerative mammals (Acomys and Oryctolagus) to determine how these cells interpret signals that normally induce cellular senescence in non-regenerating mammals (Mus and Rattus). While H2O2 exposure substantially decreases cell proliferation and increases p53, p21, p16, and p19 in cells from mice and rats, cells from spiny mice and rabbits are highly resistant to H2O2. Quantifying oxygen consumption and mitochondrial stability, we demonstrate that increased intracellular H2O2 is rapidly detoxified in regenerating species, but overwhelms antioxidant scavenging in cells from non-regenerative mammals. However, pretreatment with N-acetylcysteine (NAC) protects mouse and rat cells from ROS-induced cellular senescence. Collectively, our results show that intrinsic cellular differences in stress-sensing mechanisms partially explain interspecific variation in regenerative ability.
Argonaute bypasses cellular obstacles without hindrance during target search
Authors: Cui Tao Ju , Klein Misha , Hegge Jorrit W. , Chandradoss Stanley D. , van der Oost John , Depken Martin , Joo Chirlmin 
Published: September 2019

AbstractArgonaute (Ago) proteins are key players in both gene regulation (eukaryotes) and host defense (prokaryotes). Acting on single-stranded nucleic-acid substrates, Ago relies on base pairing between a small nucleic-acid guide and its complementary target sequences for specificity. To efficiently scan nucleic-acid chains for targets, Ago diffuses laterally along the substrate and must bypass secondary structures as well as protein barriers. Using single-molecule FRET in conjunction with kinetic modelling, we reveal that target scanning is mediated through loose protein-nucleic acid interactions, allowing Ago to slide short distances over secondary structures, as well as to bypass protein barriers via intersegmental transfer. Our combined single-molecule experiment and kinetic modelling approach may serve as a platform to dissect search processes and study the effect of sequence on search kinetics for other nucleic acid-guided proteins.
First-in-human trial of blood–brain barrier opening in amyotrophic lateral sclerosis using MR-guided focused ultrasound
Authors: Abrahao Agessandro , Meng Ying , Llinas Maheleth , Huang Yuexi , Hamani Clement , Mainprize Todd , Aubert Isabelle , Heyn Chinthaka , Black Sandra E. , Hynynen Kullervo , Lipsman Nir , Zinman Lorne 
Published: September 2019

AbstractMR-guided focused ultrasound (MRgFUS) is an emerging technology that can accurately and transiently permeabilize the blood-brain barrier (BBB) for targeted drug delivery to the central nervous system. We conducted a single-arm, first-in-human trial to investigate the safety and feasibility of MRgFUS-induced BBB opening in eloquent primary motor cortex in four volunteers with amyotrophic lateral sclerosis (ALS). Here, we show successful BBB opening using MRgFUS as demonstrated by gadolinium leakage at the target site immediately after sonication in all subjects, which normalized 24 hours later. The procedure was well-tolerated with no serious clinical, radiologic or electroencephalographic adverse events. This study demonstrates that non-invasive BBB permeabilization over the motor cortex using MRgFUS is safe, feasible, and reversible in ALS subjects. In future, MRgFUS can be coupled with promising therapeutics providing a targeted delivery platform in ALS.
Complementary vibrational spectroscopy
Authors: Hashimoto Kazuki , Badarla Venkata Ramaiah , Kawai Akira , Ideguchi Takuro 
Published: September 2019

AbstractVibrational spectroscopy, comprised of infrared absorption and Raman scattering spectroscopy, is widely used for label-free optical sensing and imaging in various scientific and industrial fields. The two molecular spectroscopy methods are sensitive to different types of vibrations and provide complementary vibrational spectra, but obtaining complete vibrational information with a single spectroscopic device is challenging due to the large wavelength discrepancy between the two methods. Here, we demonstrate simultaneous infrared absorption and Raman scattering spectroscopy that allows us to measure the complete broadband vibrational spectra in the molecular fingerprint region with a single instrument based on an ultrashort pulsed laser. The system is based on dual-modal Fourier-transform spectroscopy enabled by efficient use of nonlinear optical effects. Our proof-of-concept experiment demonstrates rapid, broadband and high spectral resolution measurements of complementary spectra of organic liquids for precise and accurate molecular analysis.
A nanofluidic device for parallel single nanoparticle catalysis in solution
Authors: Levin Sune , Fritzsche Joachim , Nilsson Sara , Runemark August , Dhokale Bhausaheb , Ström Henrik , Sundén Henrik , Langhammer Christoph , Westerlund Fredrik 
Published: September 2019

AbstractStudying single catalyst nanoparticles, during reaction, eliminates averaging effects that are an inherent limitation of ensemble experiments. It enables establishing structure–function correlations beyond averaged properties by including particle-specific descriptors such as defects, chemical heterogeneity and microstructure. Driven by these prospects, several single particle catalysis concepts have been implemented. However, they all have limitations such as low throughput, or that they require very low reactant concentrations and/or reaction rates. In response, we present a nanofluidic device for highly parallelized single nanoparticle catalysis in solution, based on fluorescence microscopy. Our device enables parallel scrutiny of tens of single nanoparticles, each isolated inside its own nanofluidic channel, and at tunable reaction conditions, ranging from the fully mass transport limited regime to the surface reaction limited regime. In a wider perspective, our concept provides a versatile platform for highly parallelized single particle catalysis in solution and constitutes a promising application area for nanofluidics.
Oncotype DX recurrence score implications for disparities in chemotherapy and breast cancer mortality in Georgia
Authors: Collin Lindsay J. , Yan Ming , Jiang Renjian , Ward Kevin C. , Crawford Brittany , Torres Mylin A. , Gogineni Keerthi , Subhedar Preeti D. , Puvanesarajah Samantha , Gaudet Mia M. , McCullough Lauren E. 
Published: September 2019

AbstractAmong women diagnosed with stage I–IIIa, node-negative, hormone receptor (HR)-positive breast cancer (BC), Oncotype DX recurrence scores (ODX RS) inform chemotherapy treatment decisions. Differences in recurrence scores or testing may contribute to racial disparities in BC mortality among women with HR+ tumors. We identified 12,081 non-Hispanic White (NHW) and non-Hispanic Black (NHB) BC patients in Georgia (2010–2014), eligible to receive an ODX RS. Logistic regression was used to estimate the odds of chemotherapy receipt by race and ODX RS. Cox proportional hazard regression was used to calculate the hazard ratios (HRs) comparing BC mortality rates by race and recurrence score. Receipt of Oncotype testing was consistent between NHB and NHW women. Receipt of chemotherapy was generally comparable within strata of ODX RS—although NHB women with low scores were slightly more likely to receive chemotherapy (OR = 1.16, 95% CI 0.77, 1.75), and NHB women with high scores less likely to receive chemotherapy (OR = 0.77, 95% CI 0.48, 1.24), than NHW counterparts. NHB women with a low recurrence score had the largest hazard of BC mortality (HR = 2.47 95% CI 1.22, 4.99) compared to NHW women. Our data suggest that additional tumor heterogeneity, or other downstream treatment factors, not captured by ODX, may be drivers of racial disparities in HR+ BC.