bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative analysis of the AIB1 interactome in breast cancer reveals MTA2 as a repressive partner which silences E-Cadherin to promote EMT and associates with a pro-metastatic phenotype
Authors: Varešlija Damir , Ward Elspeth , Purcell Siobhan P. , Cosgrove Nicola S. , Cocchiglia Sinéad , O’Halloran Philip J. , Charmsaz Sara , Bane Fiona T. , Brett Francesca M. , Farrell Michael , Cryan Jane , Beausang Alan , Hudson Lance , Turnbul Arran K. , Dixon J. Michael , Hill Arnold D. K. , Priedigkeit Nolan , Oesterreich Steffi , Lee Adrian V. , Sims Andrew H. , Redmond Aisling M. , Carroll Jason S. , Young Leonie S. 
Published: January 2021

AbstractSteroid regulated cancer cells use nuclear receptors and associated regulatory proteins to orchestrate transcriptional networks to drive disease progression. In primary breast cancer, the coactivator AIB1 promotes estrogen receptor (ER) transcriptional activity to enhance cell proliferation. The function of the coactivator in ER+ metastasis however is not established. Here we describe AIB1 as a survival factor, regulator of pro-metastatic transcriptional pathways and a promising actionable target. Genomic alterations and functional expression of AIB1 associated with reduced disease-free survival in patients and enhanced metastatic capacity in novel CDX and PDX ex-vivo models of ER+ metastatic disease. Comparative analysis of the AIB1 interactome with complementary RNAseq characterized AIB1 as a transcriptional repressor. Specifically, we report that AIB1 interacts with MTA2 to form a repressive complex, inhibiting CDH1 (encoding E-cadherin) to promote EMT and drive progression. We further report that pharmacological and genetic inhibition of AIB1 demonstrates significant anti-proliferative activity in patient-derived models establishing AIB1 as a viable strategy to target endocrine resistant metastasis. This work defines a novel role for AIB1 in the regulation of EMT through transcriptional repression in advanced cancer cells with a considerable implication for prognosis and therapeutic interventions.
Hypoxia-induced PLOD1 overexpression contributes to the malignant phenotype of glioblastoma via NF-κB signaling
Authors: Wang Zhenlin , Shi Yuping , Ying Chenting , Jiang Yang , Hu Jiangfeng 
Published: January 2021

AbstractProcollagen lysyl hydroxylase 1 (PLOD1) is highly expressed in malignant tumors such as esophageal squamous cell carcinoma, gastric cancer, and colorectal cancer. Bioinformatics analysis revealed that PLOD1 is associated with the progression of GBM, particularly the most malignant mesenchymal subtype (MES). Moreover, in the TCGA and CGGA datasets, the mean survival time of patients with high PLOD1 expression was significantly shorter than that of patients with low expression. The clinical samples confirmed this result. Therefore, we aimed to investigate the effect of PLOD1 on the development of mesenchymal GBM in vitro and in vivo and its possible mechanisms. Molecular experiments were conducted on the patient-derived glioma stem cells and found that PLOD1 expressed higher in tumor tissues and cancer cell lines of patients with GBM, especially in the MES. PLOD1 also enhanced tumor viability, proliferation, migration, and promoted MES transition while inhibited apoptosis. Tumor xenograft results also indicated that PLOD1 overexpression significantly promotes malignant behavior of tumors. Mechanistically, bioinformatics analysis further revealed that PLOD1 expression was closely associated with the NF-κB signaling pathway. Besides, we also found that hypoxic environments also enhanced the tumor-promoting effects of PLOD1. In conclusion, overexpression of PLOD1 may be an important factor in the enhanced invasiveness and MES transition of GBM. Thus, PLOD1 is a potential treatment target for mesenchymal GBM or even all GBM.
A novel role of MNT as a negative regulator of REL and the NF-κB pathway
Authors: Liaño-Pons Judit , Lafita-Navarro M. Carmen , García-Gaipo Lorena , Colomer Carlota , Rodríguez Javier , von Kriegsheim Alex , Hurlin Peter J. , Ourique Fabiana , Delgado M. Dolores , Bigas Anna , Espinosa Lluis , León Javier 
Published: January 2021

AbstractMNT, a transcription factor of the MXD family, is an important modulator of the oncoprotein MYC. Both MNT and MYC are basic-helix–loop–helix proteins that heterodimerize with MAX in a mutually exclusive manner, and bind to E-boxes within regulatory regions of their target genes. While MYC generally activates transcription, MNT represses it. However, the molecular interactions involving MNT as a transcriptional regulator beyond the binding to MAX remain unexplored. Here we demonstrate a novel MAX-independent protein interaction between MNT and REL, the oncogenic member of the NF-κB family. REL participates in important biological processes and it is altered in a variety of tumors. REL is a transcription factor that remains inactive in the cytoplasm in an inhibitory complex with IκB and translocates to the nucleus when the NF-κB pathway is activated. In the present manuscript, we show that MNT knockdown triggers REL translocation into the nucleus and thus the activation of the NF-κB pathway. Meanwhile, MNT overexpression results in the repression of IκBα, a bona fide REL target. Both MNT and REL bind to the IκBα gene on the first exon, suggesting its regulation as an MNT–REL complex. Altogether our data indicate that MNT acts as a repressor of the NF-κB pathway by two mechanisms: (1) retention of REL in the cytoplasm by MNT interaction, and (2) MNT-driven repression of REL-target genes through an MNT–REL complex. These results widen our knowledge about MNT biological roles and reveal a novel connection between the MYC/MXD and NF-κB pathways, two of the most prominent pathways in cancer.
Significant salivary changes in relation to oral mucositis following autologous hematopoietic stem cell transplantation
Authors: van Leeuwen S. J. M. , Proctor G. B. , Laheij A. M. G. A. , Potting C. M. J. , Smits O. , Bronkhorst E. M. , Hazenberg M. D. , Haverman T. M. , Brennan M. T. , von Bültzingslöwen I. , Raber-Durlacher J. E. , Huysmans M. C. D. N. J. M. , Rozema F. R. , Blijlevens N. M. A. 
Published: January 2021

AbstractThe aim of this multicentre, longitudinal study was to determine salivary changes in relation to oral mucositis (OM) in multiple myeloma patients following high-dose melphalan and autologous hematopoietic stem cell transplantation (ASCT). Unstimulated and stimulated whole-mouth saliva samples (UWS and SWS) were collected before ASCT, 1×/wk during the hospitalisation phase, and 3 and 12 months post-ASCT. During the hospitalisation period OM was scored 3×/wk (WHO system). Flow rate, pH, total protein concentration (Nanodrop), albumin, lactoferrin, neutrophil defensin-1 (HNP1), total IgA and S100A8/A9 (ELISA) were determined. Mixed models were used to evaluate differences between ulcerative (u)OM (≥2 WHO, n = 20) and non-uOM (n = 31) groups. Until 18 days after ASCT, flow rate, pH, total IgA and HNP1 levels decreased in UWS and/or SWS, while log lactoferrin levels were significantly increased (UWS: p = 0.016 95% CI [0.36, 3.58], SWS: p < 0.001 95% CI [1.14, 3.29]). Twelve months post-ASCT, salivary protein levels were similar to baseline except for log total IgA, which was higher (UWS: p < 0.001 95% CI [0.49, 1.29], SWS: p < 0.001 95% CI [0.72, 1.45]). No differences between uOM and non-uOM groups were observed. Changes in salivary proteins indicated an inflammatory reaction in salivary glands coinciding with mucosal and systemic reactions in response to high-dose melphalan.
Tailoring the d-band center of N-doped carbon nanotube arrays with Co4N nanoparticles and single-atom Co for a superior hydrogen evolution reaction
Authors: Cao Bo , Hu Minghao , Cheng Yan , Jing Peng , Liu Baocang , Zhou Bo , Wang Xi , Gao Rui , Sun Xiaolei , Du Yaping , Zhang Jun 
Published: January 2021

AbstractA 3D self-supported integrated electrode, consisting of heteroatomic nitrogen-doped carbon nanotube arrays on carbon cloth with confined ultrafine Co4N nanoparticles and a distribution of anchored single-atom Co, is fabricated via a cobalt-catalyzed growth strategy using dicyandiamide as the nitrogen and carbon source and a layered cobalt hydroxide-nitrate salt as the precursor. The abundance of exposed active sites, namely, the Co4N nanoparticles, single-atom Co, and heteroatomic N-doped carbon nanotubes, and multiple synergistic effects among these components provide suitable tailoring of thed-band center for facilitating vectorial electron transfer and efficient electrocatalysis. Benefiting from the merits of its structural features and electronic configuration, the prepared electrode exhibits robust performance toward the hydrogen evolution reaction with overpotentials of only 78 and 86 mV at 10 mA cm−2in acidic and basic electrolytes, respectively. Density functional theory calculations and X-ray photoelectron spectroscopy valence band measurements reveal that the effective tailoring of thed-band center by Co4N nanoparticles plays a crucial role in optimizing the hydrogen adsorption free energy to a more thermoneutral value for efficient electrocatalysis.
Highly stretchable metal-polymer hybrid conductors for wearable and self-cleaning sensors
Authors: Yoon Sunyoung , Kim Yong Jun , Lee Yu Rim , Lee Nae-Eung , Won Yoochan , Gandla Srinivas , Kim Sunkook , Kim Han-Ki 
Published: January 2021

AbstractWe fabricated semitransparent and stretchable hybrid Ag-polytetrafluoroethylene (PTFE) conductors on a polyurethane (PU) substrate for use in high-performance wearable and self-cleaning sensors. The highly conductive Ag metal and stretchable PTFE polymer matrix were cosputtered, embedding the self-formed Ag in the PTFE matrix. Depending on the cosputtering RF and DC power ratio, the Ag-PTFE conductors showed a sheet resistance of 3.09–17.23 Ω/square and an optical transparency of 25.27–38.49% at a wavelength of 550 nm. Under the optimal cosputtering conditions, the Ag-PTFE electrode showed outstanding stretchability (strain 20%) and reversible hysteresis, enabling the production of stretchable and semitransparent conductors. In addition, the very small critical inward/outward bending radius near 1 mm and the hydrophobic surface indicate that the Ag-PTFE films could also be applied in wearable and self-cleaning devices. The suitability of the high stretchability and low sheet resistance of the sputtered Ag-PTFE conductor was verified by using it as a stretchable interconnector for commercial ELs, LEDs, and strain sensors. We applied the Ag-PTFE film as a semitransparent conductor for stretchable touch panels and electromyography sensors. Cosputtered Ag-PTFE films are promising stretchable conductors for a variety of applications in next-generation wearable devices.
Comparison of two-drug combinations, amikacin/tigecycline/imipenem and amikacin/tigecycline/clarithromycin against Mycobacteroides abscessus subsp. abscessus using the in vitro time-kill assay
Authors: Portell-Buj Elena , Bonet-Rossinyol Queralt , López-Gavín Alexandre , Roman Angely , Fernández-Pittol Mariana , Tudó Griselda , Gonzalez-Martin Julian 
Published: January 2021

AbstractNontuberculous mycobacteria include 198 mycobacterial species. Among these, Mycobacteroides abscessus is a rapidly growing mycobacteria that causes lung and skin infections. M. abscessus lung infections are difficult to treat due to the high levels of resistance to several classes of antibiotics. The current treatment is based on combining at least two or three antibiotics. However, treatment outcomes remain very poor. The objective was to compare the in vitro activity of amikacin, tigecycline, imipenem, and clarithromycin, alone and in two different three-drug combinations (amikacin/tigecycline/imipenem and amikacin/tigecycline/clarithromycin) against seven M. abscessus subsp. abscessus clinical isolates using the time-kill assay. The two combinations showed greater activity than the antibiotics tested individually. Even though both combinations showed similar activity as well as no antagonistic activity, the combination including imipenem could not be an alternative treatment against M. abscessus subsp. abscessus lung infections caused by clarithromycin susceptible isolates. However, this combination could be considered against clarithromycin resistant isolates. Future studies are necessary to confirm this hypothesis.
Chromosome-scale genome assembly provides insights into the evolution and flavor synthesis of passion fruit (Passiflora edulis Sims)
Authors: Xia Zhiqiang , Huang Dongmei , Zhang Shengkui , Wang Wenquan , Ma Funing , Wu Bin , Xu Yi , Xu Bingqiang , Chen Di , Zou Meiling , Xu Huanyu , Zhou Xincheng , Zhan Rulin , Song Shun 
Published: January 2021

AbstractPassion fruit (Passiflora edulis Sims) is an economically valuable fruit that is cultivated in tropical and subtropical regions of the world. Here, we report an ~1341.7 Mb chromosome-scale genome assembly of passion fruit, with 98.91% (~1327.18 Mb) of the assembly assigned to nine pseudochromosomes. The genome includes 23,171 protein-coding genes, and most of the assembled sequences are repetitive sequences, with long-terminal repeats (LTRs) being the most abundant. Phylogenetic analysis revealed that passion fruit diverged after Brassicaceae and before Euphorbiaceae. Ks analysis showed that two whole-genome duplication events occurred in passion fruit at 65 MYA and 12 MYA, which may have contributed to its large genome size. An integrated analysis of genomic, transcriptomic, and metabolomic data showed that ‘alpha-linolenic acid metabolism’, ‘metabolic pathways’, and ‘secondary metabolic pathways’ were the main pathways involved in the synthesis of important volatile organic compounds (VOCs) in passion fruit, and this analysis identified some candidate genes, including GDP-fucose Transporter 1-like, Tetratricopeptide repeat protein 33, protein NETWORKED 4B isoform X1, and Golgin Subfamily A member 6-like protein 22. In addition, we identified 13 important gene families in fatty acid pathways and eight important gene families in terpene pathways. Gene family analysis showed that the ACX, ADH, ALDH, and HPL gene families, especially ACX13/14/15/20, ADH13/26/33, ALDH1/4/21, and HPL4/6, were the key genes for ester synthesis, while the TPS gene family, especially PeTPS2/3/4/24, was the key gene family for terpene synthesis. This work provides insights into genome evolution and flavor trait biology and offers valuable resources for the improved cultivation of passion fruit.
Lossless integration of multiple electronic health records for identifying pleiotropy using summary statistics
Authors: Li Ruowang , Duan Rui , Zhang Xinyuan , Lumley Thomas , Pendergrass Sarah , Bauer Christopher , Hakonarson Hakon , Carrell David S. , Smoller Jordan W. , Wei Wei-Qi , Carroll Robert , Velez Edwards Digna R. , Wiesner Georgia , Sleiman Patrick , Denny Josh C. , Mosley Jonathan D. , Ritchie Marylyn D. , Chen Yong , Moore Jason H. 
Published: January 2021

AbstractIncreasingly, clinical phenotypes with matched genetic data from bio-bank linked electronic health records (EHRs) have been used for pleiotropy analyses. Thus far, pleiotropy analysis using individual-level EHR data has been limited to data from one site. However, it is desirable to integrate EHR data from multiple sites to improve the detection power and generalizability of the results. Due to privacy concerns, individual-level patients’ data are not easily shared across institutions. As a result, we introduce Sum-Share, a method designed to efficiently integrate EHR and genetic data from multiple sites to perform pleiotropy analysis. Sum-Share requires only summary-level data and one round of communication from each site, yet it produces identical test statistics compared with that of pooled individual-level data. Consequently, Sum-Share can achieve lossless integration of multiple datasets. Using real EHR data from eMERGE, Sum-Share is able to identify 1734 potential pleiotropic SNPs for five cardiovascular diseases.
Nanoscale coordination polymers induce immunogenic cell death by amplifying radiation therapy mediated oxidative stress
Authors: Huang Zhusheng , Wang Yuxiang , Yao Dan , Wu Jinhui , Hu Yiqiao , Yuan Ahu 
Published: January 2021

AbstractRadiation therapy can potentially induce immunogenic cell death, thereby priming anti-tumor adaptive immune responses. However, radiation-induced systemic immune responses are very rare and insufficient to meet clinical needs. Here, we demonstrate a synergetic strategy for boosting radiation-induced immunogenic cell death by constructing gadolinium-hemin based nanoscale coordination polymers to simultaneously perform X-ray deposition and glutathione depletion. Subsequently, immunogenic cell death is induced by sensitized radiation to potentiate checkpoint blockade immunotherapies against primary and metastatic tumors. In conclusion, nanoscale coordination polymers-sensitized radiation therapy exhibits biocompatibility and therapeutic efficacy in preclinical cancer models, and has the potential for further application in cancer radio-immunotherapy.
Groundwater discharge impacts marine isotope budgets of Li, Mg, Ca, Sr, and Ba
Authors: Mayfield Kimberley K. , Eisenhauer Anton , Santiago Ramos Danielle P. , Higgins John A. , Horner Tristan J. , Auro Maureen , Magna Tomas , Moosdorf Nils , Charette Matthew A. , Gonneea Meagan Eagle , Brady Carolyn E. , Komar Nemanja , Peucker-Ehrenbrink Bernhard , Paytan Adina 
Published: January 2021

AbstractGroundwater-derived solute fluxes to the ocean have long been assumed static and subordinate to riverine fluxes, if not neglected entirely, in marine isotope budgets. Here we present concentration and isotope data for Li, Mg, Ca, Sr, and Ba in coastal groundwaters to constrain the importance of groundwater discharge in mediating the magnitude and isotopic composition of terrestrially derived solute fluxes to the ocean. Data were extrapolated globally using three independent volumetric estimates of groundwater discharge to coastal waters, from which we estimate that groundwater-derived solute fluxes represent, at a minimum, 5% of riverine fluxes for Li, Mg, Ca, Sr, and Ba. The isotopic compositions of the groundwater-derived Mg, Ca, and Sr fluxes are distinct from global riverine averages, while Li and Ba fluxes are isotopically indistinguishable from rivers. These differences reflect a strong dependence on coastal lithology that should be considered a priority for parameterization in Earth-system models.
An efficient and stable solar flow battery enabled by a single-junction GaAs photoelectrode
Authors: Fu Hui-Chun , Li Wenjie , Yang Ying , Lin Chun-Ho , Veyssal Atilla , He Jr-Hau , Jin Song 
Published: January 2021

AbstractConverting and storing solar energy and releasing it on demand by using solar flow batteries (SFBs) is a promising way to address the challenge of solar intermittency. Although high solar-to-output electricity efficiencies (SOEE) have been recently demonstrated in SFBs, the complex multi-junction photoelectrodes used are not desirable for practical applications. Here, we report an efficient and stable integrated SFB built with back-illuminated single-junction GaAs photoelectrode with an n-p-n sandwiched design. Rational potential matching simulation and operating condition optimization of this GaAs SFB lead to a record SOEE of 15.4% among single-junction SFB devices. Furthermore, the TiO2 protection layer and robust redox couples in neutral pH electrolyte enable the SFB to achieve stable cycling over 408 h (150 cycles). These results advance the utilization of more practical solar cells with higher photocurrent densities but lower photovoltages for high performance SFBs and pave the way for developing practical and efficient SFBs.
Van Hove singularity in the magnon spectrum of the antiferromagnetic quantum honeycomb lattice
Authors: Sala G. , Stone M. B. , Rai Binod K. , May A. F. , Laurell Pontus , Garlea V. O. , Butch N. P. , Lumsden M. D. , Ehlers G. , Pokharel G. , Podlesnyak A. , Mandrus D. , Parker D. S. , Okamoto S. , Halász Gábor B. , Christianson A. D. 
Published: January 2021

AbstractIn quantum magnets, magnetic moments fluctuate heavily and are strongly entangled with each other, a fundamental distinction from classical magnetism. Here, with inelastic neutron scattering measurements, we probe the spin correlations of the honeycomb lattice quantum magnet YbCl3. A linear spin wave theory with a single Heisenberg interaction on the honeycomb lattice, including both transverse and longitudinal channels of the neutron response, reproduces all of the key features in the spectrum. In particular, we identify a Van Hove singularity, a clearly observable sharp feature within a continuum response. The demonstration of such a Van Hove singularity in a two-magnon continuum is important as a confirmation of broadly held notions of continua in quantum magnetism and additionally because analogous features in two-spinon continua could be used to distinguish quantum spin liquids from merely disordered systems. These results establish YbCl3 as a benchmark material for quantum magnetism on the honeycomb lattice.
Bayesian genome scale modelling identifies thermal determinants of yeast metabolism
Authors: Li Gang , Hu Yating , Jan Zrimec  , Luo Hao , Wang Hao , Zelezniak Aleksej , Ji Boyang , Nielsen Jens 
Published: January 2021

AbstractThe molecular basis of how temperature affects cell metabolism has been a long-standing question in biology, where the main obstacles are the lack of high-quality data and methods to associate temperature effects on the function of individual proteins as well as to combine them at a systems level. Here we develop and apply a Bayesian modeling approach to resolve the temperature effects in genome scale metabolic models (GEM). The approach minimizes uncertainties in enzymatic thermal parameters and greatly improves the predictive strength of the GEMs. The resulting temperature constrained yeast GEM uncovers enzymes that limit growth at superoptimal temperatures, and squalene epoxidase (ERG1) is predicted to be the most rate limiting. By replacing this single key enzyme with an ortholog from a thermotolerant yeast strain, we obtain a thermotolerant strain that outgrows the wild type, demonstrating the critical role of sterol metabolism in yeast thermosensitivity. Therefore, apart from identifying thermal determinants of cell metabolism and enabling the design of thermotolerant strains, our Bayesian GEM approach facilitates modelling of complex biological systems in the absence of high-quality data and therefore shows promise for becoming a standard tool for genome scale modeling.