bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caspase-11-mediated tubular epithelial pyroptosis underlies contrast-induced acute kidney injury
Authors: Zhang Zhen , Shao Xinghua , Jiang Na , Mou Shan , Gu Leyi , Li Shu , Lin Qisheng , He Yipei , Zhang Minfang , Zhou Wenyan , Ni Zhaohui 
Published: September 2018

AbstractContrast-induced acute kidney injury (CI-AKI) is a serious complication in patients after administration of iodinated contrast media and is associated with a significant high risk for severe renal failure and death due to the wholesale necrosis of the tubules and interstitial inflammation. Pyroptosis is a form of programmed lytic cell death that is triggered by inflammatory caspases, but little is known about its role in tubular epithelial cell (TEC) death and contrast-induced acute kidney injury. Here we show that systemic exposure to contrast media causes severe tubular epithelial pyroptosis that is mediated by the inflammatory caspases, caspases 4/5 in human TECs, or the murine homolog caspase-11 in mice in vivo and in mouse TECs in vitro. Knockdown of caspase-4/5 preserved human TECs from cell death and reduced the release of mature IL-1β, and in caspase-11-deficient mice, contrast-induced acute kidney injury was abrogated, indicating a central role for caspase-11 in acute kidney injury. In addition, deletion of caspase-11 in TECs reduced Gsdmd cleavage, which is the key process for execution of pyroptosis. These results establish the requisite role of epithelial pyroptosis in contrast-induced acute kidney injury and suggest that epithelial inflammatory caspases are an important therapeutic target for acute kidney injury.
MARVELD1 depletion leads to dysfunction of motor and cognition via regulating glia-dependent neuronal migration during brain development
Authors: Liu Weizhe , Han Fang , Qu Shuai , Yao Yuanfei , Zhao Jianxiang , Akhtar Muhammad Luqman , Ci Yanpeng , Zhang Hao , Li Hongfei , Zhao Yufang , Yue Lei , Zhang Yao , Wang Changlin , Li Yu 
Published: September 2018

AbstractThe establishment of functional neuronal connectivity is dependent on the neuronal migration and the accurate positioning of neurons in the developing brain. Abnormal neuronal migration can trigger neuronal maturation defects and apoptosis. However, many genetic bases remain unclear in neuronal migration disorders during brain development. In this study, we reported that MARVELD1-defected mice displayed motor and cognitive dysfunction resulting from aberrant neuronal migration during brain development. The laminar organization of the cerebral cortex and cerebellum in MARVELD1 knockout (KO) mice is disrupted, indicating impaired radial neuronal migration. Furthermore, we used the cerebellum as a model to explore the radial neuronal migration processes, and the results demonstrated that the proper neuronal migration depended on MARVELD1 expression in glial cells of the developing brain. MARVELD1 suppressed the expression of ITGB1 and FAK Tyr397 phosphorylation in glia-dependent manner. The inhibition of the MARVELD1/ITGB1/FAK signalling pathway in MARVELD1 KO mice could reverse the defects in neuronal migration in vitro. Our findings revealed that MARVELD1 regulated neuronal migration by mediating the formation of glial fibres and ITGB1/FAK signalling pathway. The depletion of MARVELD1 during mouse brain development led to the abnormity of motor and cognition functions.
Silencing long non-coding RNA Kcnq1ot1 alleviates pyroptosis and fibrosis in diabetic cardiomyopathy
Authors: Yang Fan , Qin Ying , Lv Jie , Wang Yueqiu , Che Hui , Chen Xi , Jiang Yanan , Li Anqi , Sun Xi , Yue Er , Ren Long , Li Yang , Bai Yunlong , Wang Lihong 
Published: September 2018

AbstractDiabetes cardiomyopathy (DCM) is a critical complication of long-term chronic diabetes mellitus and is characterized by myocardial fibrosis and myocardial hypertrophy. It has been suggested that DCM is related to pyroptosis, a programmed cell death associated with inflammation. The long non-coding RNA Kcnq1ot1 is involved in different pathophysiological mechanisms of multiple diseases, including acute myocardial damage and arrhythmia. Our previous study found that Kcnq1ot1 was elevated in left ventricular tissue of diabetic mice. However, whether Kcnq1ot1 is capable of regulating pyroptosis and fibrosis in high glucose-treated cardiac fibroblasts remains unknown. The aim of the study was to investigate the mechanisms of Kcnq1ot1 in DCM. Our study revealed that silencing Kcnq1ot1 by a lentivirus-shRNA improved cardiac function and fibrosis, ameliorated pyroptosis, and inhibited TGF-β1/smads pathway in C57BL/6 mice. In vitro, experiments revealed that Kcnq1ot1 and pyroptosis were activated in cardiac fibroblasts treated with 30 mmol/l glucose. Furthermore, Kcnq1ot1 knockdown by a small interfering RNA decreased caspase-1 expression. Bioinformatic prediction and luciferase assays showed that Kcnq1ot1 functioned as a competing endogenous RNA to regulate the expression of caspase-1 by sponging miR-214-3p. In addition, silencing Kcnq1ot1 promoted gasdermin D cleavage and the secretion of IL-1β, thus repressing the TGF-β1/smads pathway in high glucose-treated cardiac fibroblasts through miR-214-3p and caspase-1. Therefore, Kcnq1ot1/miR-214-3p/caspase-1/TGF-β1 signal pathway presents a new mechanism of DCM progression and could potentially be a novel therapeutic target.
Enah overexpression is correlated with poor survival and aggressive phenotype in gastric cancer
Authors: Chen Di , Xu Li , Li Xiaowei , Chu Yi , Jiang Mingzuo , Xu Bing , Zhao Min , Wang Weijie , Wang Hua , Kang Huijie , Wang Kai , Wu Kaichun , Liang Jie , Ren Gui 
Published: September 2018

AbstractEnabled homolog (Enah), which is a member of the Ena/VASP family that also includes VASP (vasodilator-stimulated phosphoprotein) and Ena/VASP like, is a mammalian ortholog of Drosophila Enabled (Ena). An increasing number of studies demonstrated Enah overexpression is involved in human colorectal carcinomas, breast cancers and hepatocellular carcinoma. However, the significance of Enah expression in gastric cancer (GC) is poorly elucidated. Here, we demonstrate that Enah is upregulated in GC and associated with AJCC stage, depth of invasion and poor overall survival (OS). Knockdown of Enah inhibited GC cell proliferation and metastasis and vice versa. Further experiments suggested that p-Erk1/2, p-AKT, p-p65, Vimentin and Fibronectin were downregulated and E-cadherin was upregulated after Enah silencing, implicating altered functions in GC proliferation and metastasis. Thus, our study suggests that Enah is a harmful factor for GC and a novel target for GC treatment.
USP24 induces IL-6 in tumor-associated microenvironment by stabilizing p300 and β-TrCP and promotes cancer malignancy
Authors: Wang Yi-Chang , Wu Yu-Syuan , Hung Chia-Yang , Wang Shao-An , Young Ming-Jer , Hsu Tsung-I , Hung Jan-Jong 
Published: September 2018

AbstractWe have previously demonstrated that USP24 is involved in cancer progression. Here, we found that USP24 expression is upregulated in M2 macrophages and lung cancer cells. Conditioned medium from USP24-knockdown M2 macrophages decreases the migratory and chemotactic activity of lung cancer cells and the angiogenic properties of human microvascular endothelial cell 1 (HMEC-1). IL-6 expression is significantly decreased in USP24-knockdown M2 macrophages and lung cancer cells, and IL-6-replenished conditioned medium restores the migratory, chemotactic and angiogenetic properties of the cells. USP24 stabilizes p300 and β-TrCP to increase the levels of histone-3 acetylation and NF-κB, and decreases the levels of DNMT1 and IκB, thereby increasing IL-6 transcription in M2 macrophages and lung cancer cells, results in cancer malignancy finally. IL-6 has previously been a target for cancer drug development. Here, we provide direct evidence to support that USP24 promotes IL-6 expression, which might be beneficial for cancer therapy.
A unique intracellular tyrosine in neuroligin-1 regulates AMPA receptor recruitment during synapse differentiation and potentiation
Authors: Letellier Mathieu , Szíber Zsófia , Chamma Ingrid , Saphy Camille , Papasideri Ioanna , Tessier Béatrice , Sainlos Matthieu , Czöndör Katalin , Thoumine Olivier 
Published: September 2018

AbstractTo better understand the molecular mechanisms by which early neuronal connections mature into synapses, we examined the impact of neuroligin-1 (Nlg1) phosphorylation on synapse differentiation, focusing on a unique intracellular tyrosine (Y782), which differentially regulates Nlg1 binding to PSD-95 and gephyrin. By expressing Nlg1 point mutants (Y782A/F) in hippocampal neurons, we show using imaging and electrophysiology that Y782 modulates the recruitment of functional AMPA receptors (AMPARs). Nlg1-Y782F impaired both dendritic spine formation and AMPAR diffusional trapping, but not NMDA receptor recruitment, revealing the assembly of silent synapses. Furthermore, replacing endogenous Nlg1 with either Nlg1-Y782A or -Y782F in CA1 hippocampal neurons impaired long-term potentiation (LTP), demonstrating a critical role of AMPAR synaptic retention. Screening of tyrosine kinases combined with pharmacological inhibitors point to Trk family members as major regulators of endogenous Nlg1 phosphorylation and synaptogenic function. Thus, Nlg1 tyrosine phosphorylation signaling is a critical event in excitatory synapse differentiation and LTP.
Insights into a dual function amide oxidase/macrocyclase from lankacidin biosynthesis
Authors: Dorival Jonathan , Risser Fanny , Jacob Christophe , Collin Sabrina , Dräger Gerald , Paris Cédric , Chagot Benjamin , Kirschning Andreas , Gruez Arnaud , Weissman Kira J. 
Published: September 2018

AbstractAcquisition of new catalytic activity is a relatively rare evolutionary event. A striking example appears in the pathway to the antibiotic lankacidin, as a monoamine oxidase (MAO) family member, LkcE, catalyzes both an unusual amide oxidation, and a subsequent intramolecular Mannich reaction to form the polyketide macrocycle. We report evidence here for the molecular basis for this dual activity. The reaction sequence involves several essential active site residues and a conformational change likely comprising an interdomain hinge movement. These features, which have not previously been described in the MAO family, both depend on a unique dimerization mode relative to all structurally characterized members. Taken together, these data add weight to the idea that designing new multifunctional enzymes may require changes in both architecture and catalytic machinery. Encouragingly, however, our data also show LkcE to bind alternative substrates, supporting its potential utility as a general cyclization catalyst in synthetic biology.
Clonal dynamics in osteosarcoma defined by RGB marking
Authors: Gambera Stefano , Abarrategi Ander , González-Camacho Fernando , Morales-Molina Álvaro , Roma Josep , Alfranca Arantzazu , García-Castro Javier 
Published: September 2018

AbstractOsteosarcoma is a type of bone tumour characterized by considerable levels of phenotypic heterogeneity, aneuploidy, and a high mutational rate. The life expectancy of osteosarcoma patients has not changed during the last three decades and thus much remains to be learned about the disease biology. Here, we employ a RGB-based single-cell tracking system to study the clonal dynamics occurring in a de novo-induced murine osteosarcoma model. We show that osteosarcoma cells present initial polyclonal dynamics, followed by clonal dominance associated with adaptation to the microenvironment. Interestingly, the dominant clones are composed of subclones with a similar tumour generation potential when they are re-implanted in mice. Moreover, individual spontaneous metastases are clonal or oligoclonal, but they have a different cellular origin than the dominant clones present in primary tumours. In summary, we present evidence that osteosarcomagenesis can follow a neutral evolution model, in which different cancer clones coexist and propagate simultaneously.
Superplasticity in an organic crystal
Authors: Takamizawa Satoshi , Takasaki Yuichi , Sasaki Toshiyuki , Ozaki Noriaki 
Published: September 2018

AbstractSuperplasticity, which enables processing on hard-to-work solids, has been recognized only in metallic solids. While metallic materials and plastics (polymer solids) essentially possess high plastic workability, functional crystalline solids present difficulties in molding. Organic crystals especially are fragile, in the common view, and they are far from the stage of materials development. From the viewpoint of practical application; however, organic crystals are especially attractive because they are composed of ubiquitous elements and often exhibit higher performance than metallic materials. Thus, finding superplastic deformation of organic crystals, especially in a single-crystal-to-single-crystal manner, will pave the way for their material applications. This study confirmed superplasticity in a crystal of a simple organic compound: N,N-dimethyl-4-nitroaniline. The crystal exhibits single-crystal-to-single-crystal superplastic deformation without heating. This finding of “organosuperplasticity” will contribute to the future design of functional solids that do not lose their crystalline quality in molding.
Curvotaxis directs cell migration through cell-scale curvature landscapes
Authors: Pieuchot Laurent , Marteau Julie , Guignandon Alain , Dos Santos Thomas , Brigaud Isabelle , Chauvy Pierre-François , Cloatre Thomas , Ponche Arnaud , Petithory Tatiana , Rougerie Pablo , Vassaux Maxime , Milan Jean-Louis , Tusamda Wakhloo Nayana , Spangenberg Arnaud , Bigerelle Maxence , Anselme Karine 
Published: September 2018

AbstractCells have evolved multiple mechanisms to apprehend and adapt finely to their environment. Here we report a new cellular ability, which we term “curvotaxis” that enables the cells to respond to cell-scale curvature variations, a ubiquitous trait of cellular biotopes. We develop ultra-smooth sinusoidal surfaces presenting modulations of curvature in all directions, and monitor cell behavior on these topographic landscapes. We show that adherent cells avoid convex regions during their migration and position themselves in concave valleys. Live imaging combined with functional analysis shows that curvotaxis relies on a dynamic interplay between the nucleus and the cytoskeleton—the nucleus acting as a mechanical sensor that leads the migrating cell toward concave curvatures. Further analyses show that substratum curvature affects focal adhesions organization and dynamics, nuclear shape, and gene expression. Altogether, this work identifies curvotaxis as a new cellular guiding mechanism and promotes cell-scale curvature as an essential physical cue.
Robust quantum valley Hall effect for vortices in an interacting bosonic quantum fluid
Authors: Bleu O. , Malpuech G. , Solnyshkov D. D. 
Published: September 2018

AbstractTopologically protected pseudospin transport, analogous to the quantum spin Hall effect, cannot be strictly implemented for photons and in general bosons because of the lack of symmetry-protected pseudospins. Here we show that the required protection can be provided by the real-space topological excitation of an interacting quantum fluid: a quantum vortex. We consider a Bose-Einstein condensate at the Γ point of the Brillouin zone of a quantum valley Hall system based on two staggered honeycomb lattices. We demonstrate the existence of a coupling between the vortex winding and the valley of the bulk Bloch band. This leads to chiral vortex propagation on each side of the zigzag interface between two regions of inverted staggering. The topological protection provided by the vortex winding prevents valley pseudospin mixing and resonant backscattering, allowing a truly topologically protected valley pseudospin transport.
Atomically precise graphene etch stops for three dimensional integrated systems from two dimensional material heterostructures
Authors: Son Jangyup , Kwon Junyoung , Kim SunPhil , Lv Yinchuan , Yu Jaehyung , Lee Jong-Young , Ryu Huije , Watanabe Kenji , Taniguchi Takashi , Garrido-Menacho Rita , Mason Nadya , Ertekin Elif , Huang Pinshane Y. , Lee Gwan-Hyoung , M. van der Zande Arend 
Published: September 2018

AbstractAtomically precise fabrication methods are critical for the development of next-generation technologies. For example, in nanoelectronics based on van der Waals heterostructures, where two-dimensional materials are stacked to form devices with nanometer thicknesses, a major challenge is patterning with atomic precision and individually addressing each molecular layer. Here we demonstrate an atomically thin graphene etch stop for patterning van der Waals heterostructures through the selective etch of two-dimensional materials with xenon difluoride gas. Graphene etch stops enable one-step patterning of sophisticated devices from heterostructures by accessing buried layers and forming one-dimensional contacts. Graphene transistors with fluorinated graphene contacts show a room temperature mobility of 40,000 cm2 V−1 s−1 at carrier density of 4 × 1012 cm−2 and contact resistivity of 80 Ω·μm. We demonstrate the versatility of graphene etch stops with three-dimensionally integrated nanoelectronics with multiple active layers and nanoelectromechanical devices with performance comparable to the state-of-the-art.
Intracellular nucleosomes constrain a DNA linking number difference of −1.26 that reconciles the Lk paradox
Authors: Segura Joana , Joshi Ricky S. , Díaz-Ingelmo Ofelia , Valdés Antonio , Dyson Silvia , Martínez-García Belén , Roca Joaquim 
Published: September 2018

AbstractThe interplay between chromatin structure and DNA topology is a fundamental, yet elusive, regulator of genome activities. A paradigmatic case is the “linking number paradox” of nucleosomal DNA, which refers to the incongruence between the near two left-handed superhelical turns of DNA around the histone octamer and the DNA linking number difference (∆Lk) stabilized by individual nucleosomes, which has been experimentally estimated to be about −1.0. Here, we analyze the DNA topology of a library of mononucleosomes inserted into small circular minichromosomes to determine the average ∆Lkrestrained by individual nucleosomes in vivo. Our results indicate that most nucleosomes stabilize about −1.26 units of ∆Lk. This value balances the twist (∆Tw ≈ + 0.2) and writhe (∆Wr ≈ −1.5) deformations of nucleosomal DNA in terms of the equation ∆Lk = ∆Tw + ∆Wr. Our finding reconciles the existing discrepancy between theoretical and observed measurement of the ΔLkconstrained by nucleosomes.
Predicting wave overtopping thresholds on coral reef-island shorelines with future sea-level rise
Authors: Beetham E. , Kench P. S. 
Published: September 2018

AbstractWave-driven flooding is a serious hazard on coral reef-fringed coastlines that will be exacerbated by global sea-level rise. Despite the global awareness of atoll island vulnerability, little is known about the physical processes that control wave induced flooding on reef environments. To resolve the primary controls on wave-driven flooding at present and future sea levels, we present a globally applicable method for calculating wave overtopping thresholds on reef coastlines. A unique dataset of 60,000 fully nonlinear wave transformation simulations representing a wide range of wave energy, morphology and sea levels conditions was analysed to develop a tool for exploring the future trajectory of atoll island vulnerability to sea-level rise. The proposed reef-island overtopping threshold (RIOT) provides a widely applicable first-order assessment of reef-coast vulnerability to wave hazards with sea-level. Future overtopping thresholds identified for different atoll islands reveal marked spatial variability and highlight distinct morphological characteristics that enhance coastal resilience.
Malaria vaccine candidate based on Duffy-binding protein elicits strain transcending functional antibodies in a Phase I trial
Authors: Singh Kavita , Mukherjee Paushali , Shakri Ahmad Rushdi , Singh Ankita , Pandey Gaurav , Bakshi Meenakshi , Uppal Geetanjali , Jena Rajender , Rawat Ankita , Kumar Purnima , Bhardwaj Rukmini , Yazdani Syed Shams , Hans Dhiraj , Mehta Shantanu , Srinivasan Ajay , Anil K. , Madhusudhan R. L. , Patel Jaya , Singh Amit , Rao Rajeshwar , Gangireddy Santosh , Patil Rudrappa , Kaviraj Swarnendu , Singh Sanjay , Carter Darrick , Reed Steve , Kaslow David C. , Birkett Ashley , Chauhan Virander S. , Chitnis Chetan E. 
Published: September 2018

AbstractReticulocyte invasion by Plasmodium vivax requires interaction of the Duffy-binding protein (PvDBP) with host Duffy antigen receptor for chemokines (DARCs). The binding domain of PvDBP maps to a cysteine-rich region referred to as region II (PvDBPII). Blocking this interaction offers a potential path to prevent P. vivax blood-stage growth and P. vivax malaria. This forms the rationale for development of a vaccine based on PvDBPII. Here we report results of a Phase I randomized trial to evaluate the safety and immunogenicity of recombinant PvDBPII formulated with glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE). Thirty-six malaria-naive, healthy Indian male subjects aged 18–45 years were assigned into three cohorts corresponding to doses of 10, 25 and 50 µg of PvDBPII formulated with 5 µg of GLA-SE. Each cohort included nine PvDBPII/GLA-SE vaccinees and three hepatitis B control vaccine recipients. Each subject received the assigned vaccine intramuscularly on days 0, 28 and 56, and was followed up till day 180. No serious AE was reported and PvDBPII/GLA-SE was well-tolerated and safe. Analysis by ELISA showed that all three doses of PvDBPII elicited antigen-specific binding-inhibitory antibodies. The 50 µg dose elicited antibodies against PvDBPII that had the highest binding-inhibitory titres and were most persistent. Importantly, the antibody responses were strain transcending and blocked receptor binding of diverse PvDBP alleles. These results support further clinical development of PvDBPII/GLA-SE to evaluate efficacy against sporozoite or blood-stage challenge in controlled human malaria infection (CHMI) models and against natural P. vivax challenge in malaria endemic areas.