bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circular RNA GLIS2 promotes colorectal cancer cell motility via activation of the NF-κB pathway
Authors: Chen Junxiong , Yang Xiangling , Liu Ruixian , Wen Chuangyu , Wang Huihui , Huang Lanlan , Li Weiqian , Zhu Zefeng , Zhu Yonglin , Liu Huanliang 
Published: September 2020

AbstractCircular RNAs (circRNAs) are a newly discovered type of biological molecule that belongs to the noncoding RNA family. Abundant evidence has shown that circRNAs are involved in the progression of various cancers. However, the particular functions of circRNAs in colorectal cancer (CRC) remain elusive. In this study, we investigated the differentially expressed circRNAs in three pairs of cancer tissue and adjacent normal tissue of CRC. We revealed that circGLIS2 expression was higher in CRC tissue and cell lines. Gain-and-loss function assays showed that circGLIS2 was involved in the regulation of cell migration. Moreover, overexpressing circGLIS2 in CRC cells activated the NF-κB pathway and induced pro-inflammatory chemokine production, which evoked tumor-associated inflammation through recruiting leukocytes. In turn, when the cancer cells were exposed to the supernatant of circGLIS2 overexpressed cancer cells, they were endowed with the ability of migration and chemokines production. Furthermore, the rescue assay confirmed that circGLIS2 activated NF-κB signaling and promoted cell migration by sponging miR-671. Overall, our study reveals that circGLIS2, acting as a potential oncogene, maintains the abnormal activation state of the NF-κB signaling pathway via the miR-671 sponge mechanism in CRC cells. This study provides a scientific basis for targeting circGLIS2 in colorectal cancer interventions.
Together we stand, apart we fall: how cell-to-cell contact/interplay provides resistance to ferroptosis
Authors: Vucetic Milica , Daher Boutaina , Cassim Shamir , Meira Willian , Pouyssegur Jacques 
Published: September 2020

AbstractContextualisation of the new type of cell death called “ferroptosis” opened a completely new avenue for the development of anti-cancer therapies. Cumulative fundamental research dating back to the mid-20th century, crowned by the extraordinary work of the group led by Dr. Stockwell from Columbia University in 2012, finally got its candidature to be applied in the clinical settings. Although the potential for clinical importance is undoubtedly growing every day, as showed by the increasing number of papers dealing with ferroptosis and its applications, long experience of cancer research and treatment taught us that caution is still necessary. The plasticity of the tumour cells, particularly acute, along with its involvement in the resistance mechanisms, that have been seen, to greater or lesser extent, for almost all currently used therapies, represents the biggest fascinations in biomedical research field and also the biggest challenge to achieving cures in cancer patients. Accordingly, the main features of fundamental research have to be vigilance and anticipation. In this review, we tried to summarize the literature data, accumulated in the past couple of years, which point out the pitfalls in which “ferroptosis inducers” can fall if used prematurely in the clinical settings, but at the same time can provide a great advantage in the exhausting battle with cancer resistance. This is the first comprehensive review focusing on the effects of the cell-to-cell contact/interplay in the development of resistance to ferroptosis, while the contribution of cell-born factors has been summarized previously so here we just listed them.
Terminal differentiation of human granulosa cells as luteinization is reversed by activin-A through silencing of Jnk pathway
Authors: Bildik Gamze , Akin Nazli , Esmaeilian Yashar , Hela Francesko , Yildiz Ceren Sultan , Iltumur Ece , İncir Said , Karahuseyinoglu Sercin , Yakin Kayhan , Oktem Ozgur 
Published: September 2020

AbstractMolecular mechanisms underlying luteinization (terminal differentiation of granulosa and theca cells after ovulation) and luteolysis (demise of corpus luteum) are poorly understood in human ovary. Here we report that activin-A, after binding to its cognate receptors induces a functional luteolytic state and reverses luteinization phenotype by downregulating the expression of the steroidogenic enzymes, LH receptor and VEGF and reducing estradiol (E2) progesterone (P4) production and upregulating FSH receptor and cyclin D1 expression in human primary luteinized granulosa cells. Further, this action of activin-A involves downregulation of JNK signaling pathway and is opposite to that of human chorionic gonadotropin (hCG), which acts as a luteotropic hormone and improves luteal function through the activation of JNK pathway in the same cell type. Reversal of luteinization phenotype in luteal granulosa cells by activin-A potentially makes this hormone an attractive candidate for use under certain clinical situations, where induction of luteolysis and rapid reduction of endogenous sex steroid levels are beneficial such as ovarian hyperstimulation syndrome (OHSS), in which the ovaries hyper-respond to gonadotropin stimulation by producing too many growing follicles along with development of ascites, pleural effusion, and hemo-concentrations as a result of increased vascular permeability and leakage of intravascular volume into third spaces. Our work unveils a previously undefined role for activin-A and JNK signaling pathway in human corpus luteum biology, that might have a direct clinical impact in assisted reproductive technologies.
Transcriptomic profiling of human cardiac cells predicts protein kinase inhibitor-associated cardiotoxicity
Authors: van Hasselt J. G. Coen , Rahman Rayees , Hansen Jens , Stern Alan , Shim Jaehee V. , Xiong Yuguang , Pickard Amanda , Jayaraman Gomathi , Hu Bin , Mahajan Milind , Gallo James M. , Goldfarb Joseph , Sobie Eric A. , Birtwistle Marc R. , Schlessinger Avner , Azeloglu Evren U. , Iyengar Ravi 
Published: September 2020

AbstractKinase inhibitors (KIs) represent an important class of anti-cancer drugs. Although cardiotoxicity is a serious adverse event associated with several KIs, the reasons remain poorly understood, and its prediction remains challenging. We obtain transcriptional profiles of human heart-derived primary cardiomyocyte like cell lines treated with a panel of 26 FDA-approved KIs and classify their effects on subcellular pathways and processes. Individual cardiotoxicity patient reports for these KIs, obtained from the FDA Adverse Event Reporting System, are used to compute relative risk scores. These are then combined with the cell line-derived transcriptomic datasets through elastic net regression analysis to identify a gene signature that can predict risk of cardiotoxicity. We also identify relationships between cardiotoxicity risk and structural/binding profiles of individual KIs. We conclude that acute transcriptomic changes in cell-based assays combined with drug substructures are predictive of KI-induced cardiotoxicity risk, and that they can be informative for future drug discovery.
Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma
Authors: Tseng Hsiang-chi , Xiong Wei , Badeti Saiaditya , Yang Yan , Ma Minh , Liu Ting , Ramos Carlos A. , Dotti Gianpietro , Fritzky Luke , Jiang Jie-gen , Yi Qing , Guarrera James , Zong Wei-Xing , Liu Chen , Liu Dongfang 
Published: September 2020

AbstractChimeric antigen receptor (CAR) therapy is a promising immunotherapeutic strategy for treating multiple refractory blood cancers, but further advances are required for solid tumor CAR therapy. One challenge is identifying a safe and effective tumor antigen. Here, we devise a strategy for targeting hepatocellular carcinoma (HCC, one of the deadliest malignancies). We report that T and NK cells transduced with a CAR that recognizes the surface marker, CD147, also known as Basigin, can effectively kill various malignant HCC cell lines in vitro, and HCC tumors in xenograft and patient-derived xenograft mouse models. To minimize any on-target/off-tumor toxicity, we use logic-gated (log) GPC3–synNotch-inducible CD147-CAR to target HCC. LogCD147-CAR selectively kills dual antigen (GPC3+CD147+), but not single antigen (GPC3-CD147+) positive HCC cells and does not cause severe on-target/off-tumor toxicity in a human CD147 transgenic mouse model. In conclusion, these findings support the therapeutic potential of CD147-CAR-modified immune cells for HCC patients.
Lymph node metastasis prediction of papillary thyroid carcinoma based on transfer learning radiomics
Authors: Yu Jinhua , Deng Yinhui , Liu Tongtong , Zhou Jin , Jia Xiaohong , Xiao Tianlei , Zhou Shichong , Li Jiawei , Guo Yi , Wang Yuanyuan , Zhou Jianqiao , Chang Cai 
Published: September 2020

AbstractNon-invasive assessment of the risk of lymph node metastasis (LNM) in patients with papillary thyroid carcinoma (PTC) is of great value for the treatment option selection. The purpose of this paper is to develop a transfer learning radiomics (TLR) model for preoperative prediction of LNM in PTC patients in a multicenter, cross-machine, multi-operator scenario. Here we report the TLR model produces a stable LNM prediction. In the experiments of cross-validation and independent testing of the main cohort according to diagnostic time, machine, and operator, the TLR achieves an average area under the curve (AUC) of 0.90. In the other two independent cohorts, TLR also achieves 0.93 AUC, and this performance is statistically better than the other three methods according to Delong test. Decision curve analysis also proves that the TLR model brings more benefit to PTC patients than other methods.
Probing magnetism in atomically thin semiconducting PtSe2
Authors: Avsar Ahmet , Cheon Cheol-Yeon , Pizzochero Michele , Tripathi Mukesh , Ciarrocchi Alberto , Yazyev Oleg V. , Kis Andras 
Published: September 2020

AbstractAtomic-scale disorder in two-dimensional transition metal dichalcogenides is often accompanied by local magnetic moments, which can conceivably induce long-range magnetic ordering into intrinsically non-magnetic materials. Here, we demonstrate the signature of long-range magnetic orderings in defective mono- and bi-layer semiconducting PtSe2 by performing magnetoresistance measurements under both lateral and vertical measurement configurations. As the material is thinned down from bi- to mono-layer thickness, we observe a ferromagnetic-to-antiferromagnetic crossover, a behavior which is opposite to the one observed in the prototypical 2D magnet CrI3. Our first-principles calculations, supported by aberration-corrected transmission electron microscopy imaging of point defects, associate this transition to the interplay between the defect-induced magnetism and the interlayer interactions in PtSe2. Furthermore, we show that graphene can be effectively used to probe the magnetization of adjacent semiconducting PtSe2. Our findings in an ultimately scaled monolayer system lay the foundation for atom-by-atom engineering of magnetism in otherwise non-magnetic 2D materials.
Repurposing anti-inflammasome NRTIs for improving insulin sensitivity and reducing type 2 diabetes development
Authors: Ambati Jayakrishna , Magagnoli Joseph , Leung Hannah , Wang Shao-bin , Andrews Chris A. , Fu Dongxu , Pandey Akshat , Sahu Srabani , Narendran Siddharth , Hirahara Shuichiro , Fukuda Shinichi , Sun Jian , Pandya Lekha , Ambati Meenakshi , Pereira Felipe , Varshney Akhil , Cummings Tammy , Hardin James W. , Edun Babatunde , Bennett Charles L. , Ambati Kameshwari , Fowler Benjamin J. , Kerur Nagaraj , Röver Christian , Leitinger Norbert , Werner Brian C. , Stein Joshua D. , Sutton S. Scott , Gelfand Bradley D. 
Published: September 2020

AbstractInnate immune signaling through the NLRP3 inflammasome is activated by multiple diabetes-related stressors, but whether targeting the inflammasome is beneficial for diabetes is still unclear. Nucleoside reverse-transcriptase inhibitors (NRTI), drugs approved to treat HIV-1 and hepatitis B infections, also block inflammasome activation. Here, we show, by analyzing five health insurance databases, that the adjusted risk of incident diabetes is 33% lower in patients with NRTI exposure among 128,861 patients with HIV-1 or hepatitis B (adjusted hazard ratio for NRTI exposure, 0.673; 95% confidence interval, 0.638 to 0.710; P < 0.0001; 95% prediction interval, 0.618 to 0.734). Meanwhile, an NRTI, lamivudine, improves insulin sensitivity and reduces inflammasome activation in diabetic and insulin resistance-induced human cells, as well as in mice fed with high-fat chow; mechanistically, inflammasome-activating short interspersed nuclear element (SINE) transcripts are elevated, whereas SINE-catabolizing DICER1 is reduced, in diabetic cells and mice. These data suggest the possibility of repurposing an approved class of drugs for prevention of diabetes.
Understanding electrochemical switchability of perovskite-type exsolution catalysts
Authors: Opitz Alexander K. , Nenning Andreas , Vonk Vedran , Volkov Sergey , Bertram Florian , Summerer Harald , Schwarz Sabine , Steiger-Thirsfeld Andreas , Bernardi Johannes , Stierle Andreas , Fleig Jürgen 
Published: September 2020

AbstractExsolution of metal nanoparticles from perovskite-type oxides is a very promising approach to obtain catalysts with superior properties. One particularly interesting property of exsolution catalysts is the possibility of electrochemical switching between different activity states. In this work, synchrotron-based in-situ X-ray diffraction experiments on electrochemically polarized La0.6Sr0.4FeO3-δthin film electrodes are performed, in order to simultaneously obtain insights into the phase composition and the catalytic activity of the electrode surface. This shows that reversible electrochemical switching between a high and low activity state is accompanied by a phase change of exsolved particles between metallic α-­Fe and Fe-oxides. Reintegration of iron into the perovskite lattice is thus not required for obtaining a switchable catalyst, making this process especially interesting for intermediate temperature applications. These measurements also reveal how metallic particles on La0.6Sr0.4FeO3-δelectrodes affect the H2oxidation and H2O splitting mechanism and why the particle size plays a minor role.
Multiplatform genomic profiling and magnetic resonance imaging identify mechanisms underlying intratumor heterogeneity in meningioma
Authors: Magill Stephen T. , Vasudevan Harish N. , Seo Kyounghee , Villanueva-Meyer Javier E. , Choudhury Abrar , John Liu S. , Pekmezci Melike , Findakly Sarah , Hilz Stephanie , Lastella Sydney , Demaree Benjamin , Braunstein Steve E. , Bush Nancy Ann Oberheim , Aghi Manish K. , Theodosopoulos Philip V. , Sneed Penny K. , Abate Adam R. , Berger Mitchel S. , McDermott Michael W. , Lim Daniel A. , Ullian Erik M. , Costello Joseph F. , Raleigh David R. 
Published: September 2020

AbstractMeningiomas are the most common primary intracranial tumors, but the molecular drivers of meningioma tumorigenesis are poorly understood. We hypothesized that investigating intratumor heterogeneity in meningiomas would elucidate biologic drivers and reveal new targets for molecular therapy. To test this hypothesis, here we perform multiplatform molecular profiling of 86 spatially-distinct samples from 13 human meningiomas. Our data reveal that regional alterations in chromosome structure underlie clonal transcriptomic, epigenomic, and histopathologic signatures in meningioma. Stereotactic co-registration of sample coordinates to preoperative magnetic resonance images further suggest that high apparent diffusion coefficient (ADC) distinguishes meningioma regions with proliferating cells enriched for developmental gene expression programs. To understand the function of these genes in meningioma, we develop a human cerebral organoid model of meningioma and validate the high ADC marker genes CDH2 and PTPRZ1 as potential targets for meningioma therapy using live imaging, single cell RNA sequencing, CRISPR interference, and pharmacology.
T-Plastin reinforces membrane protrusions to bridge matrix gaps during cell migration
Authors: Garbett Damien , Bisaria Anjali , Yang Changsong , McCarthy Dannielle G. , Hayer Arnold , Moerner W. E. , Svitkina Tatyana M. , Meyer Tobias 
Published: September 2020

AbstractMigrating cells move across diverse assemblies of extracellular matrix (ECM) that can be separated by micron-scale gaps. For membranes to protrude and reattach across a gap, actin filaments, which are relatively weak as single filaments, must polymerize outward from adhesion sites to push membranes towards distant sites of new adhesion. Here, using micropatterned ECMs, we identify T-Plastin, one of the most ancient actin bundling proteins, as an actin stabilizer that promotes membrane protrusions and enables bridging of ECM gaps. We show that T-Plastin widens and lengthens protrusions and is specifically enriched in active protrusions where F-actin is devoid of non-muscle myosin II activity. Together, our study uncovers critical roles of the actin bundler T-Plastin to promote protrusions and migration when adhesion is spatially-gapped.
Particle engineering enabled by polyphenol-mediated supramolecular networks
Authors: Zhou Jiajing , Lin Zhixing , Penna Matthew , Pan Shuaijun , Ju Yi , Li Shiyao , Han Yiyuan , Chen Jingqu , Lin Gan , Richardson Joseph J. , Yarovsky Irene , Caruso Frank 
Published: September 2020

AbstractWe report a facile strategy for engineering diverse particles based on the supramolecular assembly of natural polyphenols and a self-polymerizable aromatic dithiol. In aqueous conditions, uniform and size-tunable supramolecular particles are assembled through π–π interactions as mediated by polyphenols. Owing to the high binding affinity of phenolic motifs present at the surface, these particles allow for the subsequent deposition of various materials (i.e., organic, inorganic, and hybrid components), producing a variety of monodisperse functional particles. Moreover, the solvent-dependent disassembly of the supramolecular networks enables their removal, generating a wide range of corresponding hollow structures including capsules and yolk–shell structures. The versatility of these supramolecular networks, combined with their negligible cytotoxicity provides a pathway for the rational design of a range of particle systems (including core–shell, hollow, and yolk–shell) with potential in biomedical and environmental applications.
REM sleep promotes experience-dependent dendritic spine elimination in the mouse cortex
Authors: Zhou Yanmei , Lai Cora Sau Wan , Bai Yang , Li Wei , Zhao Ruohe , Yang Guang , Frank Marcos G. , Gan Wen-Biao 
Published: September 2020

AbstractIn many parts of the nervous system, experience-dependent refinement of neuronal circuits predominantly involves synapse elimination. The role of sleep in this process remains unknown. We investigated the role of sleep in experience-dependent dendritic spine elimination of layer 5 pyramidal neurons in the visual (V1) and frontal association cortex (FrA) of 1-month-old mice. We found that monocular deprivation (MD) or auditory-cued fear conditioning (FC) caused rapid spine elimination in V1 or FrA, respectively. MD- or FC-induced spine elimination was significantly reduced after total sleep or REM sleep deprivation. Total sleep or REM sleep deprivation also prevented MD- and FC-induced reduction of neuronal activity in response to visual or conditioned auditory stimuli. Furthermore, dendritic calcium spikes increased substantially during REM sleep, and the blockade of these calcium spikes prevented MD- and FC-induced spine elimination. These findings reveal an important role of REM sleep in experience-dependent synapse elimination and neuronal activity reduction.
Massive and rapid COVID-19 testing is feasible by extraction-free SARS-CoV-2 RT-PCR
Authors: Smyrlaki Ioanna , Ekman Martin , Lentini Antonio , Rufino de Sousa Nuno , Papanicolaou Natali , Vondracek Martin , Aarum Johan , Safari Hamzah , Muradrasoli Shaman , Rothfuchs Antonio Gigliotti , Albert Jan , Högberg Björn , Reinius Björn 
Published: September 2020

AbstractCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is commonly diagnosed by reverse transcription polymerase chain reaction (RT-PCR) to detect viral RNA in patient samples, but RNA extraction constitutes a major bottleneck in current testing. Methodological simplification could increase diagnostic availability and efficiency, benefitting patient care and infection control. Here, we describe methods circumventing RNA extraction in COVID-19 testing by performing RT-PCR directly on heat-inactivated or lysed samples. Our data, including benchmarking using 597 clinical patient samples and a standardised diagnostic system, demonstrate that direct RT-PCR is viable option to extraction-based tests. Using controlled amounts of active SARS-CoV-2, we confirm effectiveness of heat inactivation by plaque assay and evaluate various generic buffers as transport medium for direct RT-PCR. Significant savings in time and cost are achieved through RNA-extraction-free protocols that are directly compatible with established PCR-based testing pipelines. This could aid expansion of COVID-19 testing.
Genetic screens reveal a central role for heme metabolism in artemisinin susceptibility
Authors: Harding Clare R. , Sidik Saima M. , Petrova Boryana , Gnädig Nina F. , Okombo John , Herneisen Alice L. , Ward Kurt E. , Markus Benedikt M. , Boydston Elizabeth A. , Fidock David A. , Lourido Sebastian 
Published: September 2020

AbstractArtemisinins have revolutionized the treatment of Plasmodium falciparum malaria; however, resistance threatens to undermine global control efforts. To broadly explore artemisinin susceptibility in apicomplexan parasites, we employ genome-scale CRISPR screens recently developed for Toxoplasma gondii to discover sensitizing and desensitizing mutations. Using a sublethal concentration of dihydroartemisinin (DHA), we uncover the putative transporter Tmem14c whose disruption increases DHA susceptibility. Screens performed under high doses of DHA provide evidence that mitochondrial metabolism can modulate resistance. We show that disrupting a top candidate from the screens, the mitochondrial protease DegP2, lowers porphyrin levels and decreases DHA susceptibility, without significantly altering parasite fitness in culture. Deleting the homologous gene in P. falciparum, PfDegP, similarly lowers heme levels and DHA susceptibility. These results expose the vulnerability of heme metabolism to genetic perturbations that can lead to increased survival in the presence of DHA.
Orthogonal colloidal quantum dot inks enable efficient multilayer optoelectronic devices
Authors: Lee Seungjin , Choi Min-Jae , Sharma Geetu , Biondi Margherita , Chen Bin , Baek Se-Woong , Najarian Amin Morteza , Vafaie Maral , Wicks Joshua , Sagar Laxmi Kishore , Hoogland Sjoerd , de Arquer F. Pelayo García , Voznyy Oleksandr , Sargent Edward H. 
Published: September 2020

AbstractSurface ligands enable control over the dispersibility of colloidal quantum dots (CQDs) via steric and electrostatic stabilization. Today’s device-grade CQD inks have consistently relied on highly polar solvents: this enables facile single-step deposition of multi-hundred-nanometer-thick CQD films; but it prevents the realization of CQD film stacks made up of CQDs having different compositions, since polar solvents redisperse underlying films. Here we introduce aromatic ligands to achieve process-orthogonal CQD inks, and enable thereby multifunctional multilayer CQD solids. We explore the effect of the anchoring group of the aromatic ligand on the solubility of CQD inks in weakly-polar solvents, and find that a judicious selection of the anchoring group induces a dipole that provides additional CQD-solvent interactions. This enables colloidal stability without relying on bulky insulating ligands. We showcase the benefit of this ink as the hole transport layer in CQD optoelectronics, achieving an external quantum efficiency of 84% at 1210 nm.