bluuebunny/crossref_metadata_2025_split huggingface dataset:
GATA3 recruits UTX for gene transcriptional activation to suppress metastasis of breast cancer
Authors: Yu Wenqian , Huang Wei , Yang Yang , Qiu Rongfang , Zeng Yi , Hou Yongqiang , Sun Gancheng , Shi Hang , Leng Shuai , Feng Dandan , Chen Yang , Wang Shuang , Teng Xu , Yu Hefen , Wang Yan 
Published: November 2019

AbstractGATA3 has emerged as a prominent transcription factor required for maintaining mammary-gland homeostasis. GATA3 loss is associated with aggressive breast cancer development, but the mechanism by which breast cancer is affected by the loss of GATA3 function remains unclear. Here, we report that GATA3 expression is positively correlated with the expression of UTX, a histone H3K27 demethylase contained in the MLL4 methyltransferase complex, and that GATA3 recruits the chromatin-remodeling MLL4 complex and interacts directly with UTX, ASH2L, and RBBP5. Using RNA sequencing and chromatin immunoprecipitation and sequencing, we demonstrate that the GATA3/UTX complex synergistically regulates a cohort of genes including Dicer and UTX, which are critically involved in the epithelial-to-mesenchymal transition (EMT). Our results further show that the GATA3-UTX-Dicer axis inhibits EMT, invasion, and metastasis of breast cancer cells in vitro and the dissemination of breast cancer in vivo. Our study implicates the GATA3-UTX-Dicer axis in breast cancer metastasis and provides new mechanistic insights into the pathophysiological function of GATA3.
Pancreatic cancer-educated macrophages protect cancer cells from complement-dependent cytotoxicity by up-regulation of CD59
Authors: Zhang Ronghua , Liu Qiaofei , Peng Junya , Wang Mengyi , Gao Xiang , Liao Quan , Zhao Yupei 
Published: November 2019

AbstractTumor-associated macrophages (TAMs) are versatile immune cells that promote a variety of malignant behaviors of pancreatic cancer. CD59 is a GPI-anchored membrane protein that prevents complement activation by inhibiting the formation of the membrane attack complex, which may protect cancer cells from complement-dependent cytotoxicity (CDC). The interactions between CD59, TAMs and pancreatic cancer remain largely unknown. A tissue microarray of pancreatic cancer patients was used to evaluate the interrelationship of CD59 and TAMs and their survival impacts were analyzed. In a coculture system, THP-1 cells were used as a model to study the function of TAMs and the roles of pancreatic cancer-educated macrophages in regulating the expression of CD59 in pancreatic cancer cells were demonstrated by real-time PCR, western blot and immunofluorescence staining. The effects of macrophages on regulating CDC in pancreatic cancer cells were demonstrated by an in vitro study. To explore the potential mechanisms, RNA sequencing of pancreatic cancer cells with or without co-culture of THP-1 macrophages was performed, and the results showed that the IL-6R/STAT3 signaling pathway might participate in the regulation, which was further demonstrated by target-siRNA transfection, antibody neutralization and STAT3 inhibitors. Our data revealed that the infiltration of TAMs and the expression of CD59 of pancreatic cancer were paralleled, and higher infiltration of TAMs and higher expression of CD59 predicted worse survival of pancreatic cancer patients. Pancreatic cancer-educated macrophages could protect cancer cells from CDC by up-regulating CD59 via the IL-6R/STAT3 signaling pathway. These findings uncovered the novel mechanisms between TAMs and CD59, and contribute to providing a new promising target for the immunotherapy of pancreatic cancer.
The paracrine induction of prostate cancer progression by caveolin-1
Authors: Lin Chun-Jung , Yun Eun-Jin , Lo U-Ging , Tai Yu-Ling , Deng Su , Hernandez Elizabeth , Dang Andrew , Chen Yu-An , Saha Debabrata , Mu Ping , Lin Ho , Li Tsai-Kun , Shen Tang-Long , Lai Chih-Ho , Hsieh Jer-Tsong 
Published: November 2019

AbstractA subpopulation of cancer stem cells (CSCs) plays a critical role of cancer progression, recurrence, and therapeutic resistance. Many studies have indicated that castration-resistant prostate cancer (CRPC) is associated with stem cell phenotypes, which could further promote neuroendocrine transdifferentiation. Although only a small subset of genetically pre-programmed cells in each organ has stem cell capability, CSCs appear to be inducible among a heterogeneous cancer cell population. However, the inductive mechanism(s) leading to the emergence of these CSCs are not fully understood in CRPC. Tumor cells actively produce, release, and utilize exosomes to promote cancer development and metastasis, cancer immune evasion as well as chemotherapeutic resistance; the impact of tumor-derived exosomes (TDE) and its cargo on prostate cancer (PCa) development is still unclear. In this study, we demonstrate that the presence of Cav-1 in TDE acts as a potent driver to induce CSC phenotypes and epithelial–mesenchymal transition in PCa undergoing neuroendocrine differentiation through NFκB signaling pathway. Furthermore, Cav-1 in mCRPC-derived exosomes is capable of inducing radio- and chemo-resistance in recipient cells. Collectively, these data support Cav-1 as a critical driver for mCRPC progression.
RBBP6, a RING finger-domain E3 ubiquitin ligase, induces epithelial–mesenchymal transition and promotes metastasis of colorectal cancer
Authors: Xiao Chao , Wu Gang , Zhou Zhijie , Zhang Xin , Wang YuPeng , Song Guohe , Ding Erxun , Sun Xing , Zhong Lin , Li Shanbao , Weng Junyong , Zhu Zhonglin , Chen Jian , Wang Xiaoliang 
Published: November 2019

AbstractRBBP6 has been implicated in tumorigenesis but its role in tumor metastasis and progression has not been evaluated. Interestingly, here we show that RBBP6 is upregulated in colorectal cancer (CRC) where its expression level is positively correlated with distant metastasis. In this study, we identified RBBP6, a RING Finger-domain E3 ubiquitin ligase, served as an independent prognostic factor and predicted poor outcome for CRC patients. RBBP6 promoted cell proliferation, migration, and invasion in CRC cells and promoted tumor growth, lung metastasis, and liver metastasis in mouse models. Mechanistically, we revealed that RBBP6 bound and ubiquitylated IκBα, an inhibitor of the NF-κB-signaling pathway. RBBP6-mediated ubiquitination and degradation of IκBα significantly enhanced p65 nuclear translocation, which triggered the activation of NF-κB pathway and then induced the epithelial–mesenchymal transition (EMT) process and cell metastasis. Furthermore, by DNA methylation results and ChIP analysis, we demonstrated that the promoter of RBBP6 was hypomethylated, and was activated by multi-oncogenic transcription factors. In conclusion, our findings suggest that RBBP6 may be a potential prognostic biomarker and therapeutic target for CRC invasion and metastasis.
A novel mouse model demonstrates that oncogenic melanocyte stem cells engender melanoma resembling human disease
Authors: Sun Qi , Lee Wendy , Mohri Yasuaki , Takeo Makoto , Lim Chae Ho , Xu Xiaowei , Myung Peggy , Atit Radhika P. , Taketo M. Mark , Moubarak Rana S. , Schober Markus , Osman Iman , Gay Denise L. , Saur Dieter , Nishimura Emi K. , Ito Mayumi 
Published: November 2019

AbstractMelanoma, the deadliest skin cancer, remains largely incurable at advanced stages. Currently, there is a lack of animal models that resemble human melanoma initiation and progression. Recent studies using a Tyr-CreER driven mouse model have drawn contradictory conclusions about the potential of melanocyte stem cells (McSCs) to form melanoma. Here, we employ a c-Kit-CreER-driven model that specifically targets McSCs to show that oncogenic McSCs are a bona fide source of melanoma that expand in the niche, and then establish epidermal melanomas that invade into the underlying dermis. Further, normal Wnt and Endothelin niche signals during hair anagen onset are hijacked to promote McSC malignant transformation during melanoma induction. Finally, molecular profiling reveals strong resemblance of murine McSC-derived melanoma to human melanoma in heterogeneity and gene signatures. These findings provide experimental validation of the human melanoma progression model and key insights into the transformation and heterogeneity of McSC-derived melanoma.
Microdroplet-guided intercalation and deterministic delamination towards intelligent rolling origami
Authors: Xu Borui , Zhang Xinyuan , Tian Ziao , Han Di , Fan Xingce , Chen Yimeng , Di Zengfeng , Qiu Teng , Mei Yongfeng 
Published: November 2019

AbstractThree-dimensional microstructures fabricated by origami, including folding, rolling and buckling, gain great interests in mechanics, optics and electronics. We propose a general strategy on on-demand and spontaneous rolling origami for artificial microstructures aiming at massive and intelligent production. Deposited nanomembranes are rolled-up in great amount triggered by the intercalation of tiny droplet, taking advantage of a creative design of van der Waals interaction with substrate. The rolling of nanomembranes delaminated by liquid permits a wide choice in materials as well as precise manipulation in rolling direction by controlling the motion of microdroplet, resulting in intelligent construction of rolling microstructures with designable geometries. Moreover, this liquid-triggered delamination phenomenon and constructed microstructures are demonstrated in the applications among vapor sensing, microresonators, micromotors, and microactuators. This investigation offers a simple, massive, low-cost, versatile and designable construction of rolling microstructures for fundamental research and practical applications.
Targeted resequencing identifies genes with recurrent variation in cerebral palsy
Authors: van Eyk C. L. , Corbett M. A. , Frank M. S. B. , Webber D. L. , Newman M. , Berry J. G. , Harper K. , Haines B. P. , McMichael G. , Woenig J. A. , MacLennan A. H. , Gecz J. 
Published: November 2019

AbstractA growing body of evidence points to a considerable and heterogeneous genetic aetiology of cerebral palsy (CP). To identify recurrently variant CP genes, we designed a custom gene panel of 112 candidate genes. We tested 366 clinically unselected singleton cases with CP, including 271 cases not previously examined using next-generation sequencing technologies. Overall, 5.2% of the naïve cases (14/271) harboured a genetic variant of clinical significance in a known disease gene, with a further 4.8% of individuals (13/271) having a variant in a candidate gene classified as intolerant to variation. In the aggregate cohort of individuals from this study and our previous genomic investigations, six recurrently hit genes contributed at least 4% of disease burden to CP:COL4A1,TUBA1A, AGAP1,L1CAM,MAOBandKIF1A. Significance of Rare VAriants (SORVA) burden analysis identified four genes with a genome-wide significant burden of variants,AGAP1,ERLIN1,ZDHHC9andPROC, of which we functionally assessedAGAP1using a zebrafish model. Our investigations reinforce that CP is a heterogeneous neurodevelopmental disorder with known as well as novel genetic determinants.
The Empusa code generator and its application to GBOL, an extendable ontology for genome annotation
Authors: van Dam Jesse C. J. , Koehorst Jasper J. , Vik Jon Olav , Martins dos Santos Vitor A. P. , Schaap Peter J. , Suarez-Diez Maria 
Published: November 2019

AbstractThe RDF data model facilitates integration of diverse data available in structured and semi-structured formats. To obtain a coherent RDF graph the chosen ontology must be consistently applied. However, addition of new diverse data causes the ontology to evolve, which could lead to accumulation of unintended erroneous composites. Thus, there is a need for a gate keeping system that compares the intended content described in the ontology with the actual content of the resource. The Empusa code generator facilitates creation of composite RDF resources from disparate sources. Empusa can convert a schema into an associated application programming interface (API), that can be used to perform data consistency checks and generates Markdown documentation to make persistent URLs resolvable. Using Empusa consistency is ensured within and between the ontology and the content of the resource. As an illustration of the potential of Empusa, we present the Genome Biology Ontology Language (GBOL). GBOL uses and extends current ontologies to provide a formal representation of genomic entities, along with their properties, relations and provenance.
Localized delivery of compounds into articular cartilage by using high-intensity focused ultrasound
Authors: Nieminen Heikki J. , Lampsijärvi Eetu , Barreto Gonçalo , Finnilä Mikko A. J. , Salmi Ari , Airaksinen Anu J. , Eklund Kari K. , Saarakkala Simo , Pritzker Kenneth P. H. , Hæggström Edward 
Published: November 2019

AbstractLocalized delivery of drugs into an osteoarthritic cartilaginous lesion does not yet exist, which limits pharmaceutical management of osteoarthritis (OA). High-intensity focused ultrasound (HIFU) provides a means to actuate matter from a distance in a non-destructive way. In this study, we aimed to deliver methylene blue locally into bovine articular cartilage in vitro. HIFU-treated samples (n = 10) were immersed in a methylene blue (MB) solution during sonication (f = 2.16 MHz, peak-positive-pressure = 3.5 MPa, mechanical index = 1.8, pulse repetition frequency = 3.0 kHz, cycles per burst: 50, duty cycle: 7%). Adjacent control 1 tissue (n = 10) was first pre-treated with HIFU followed by immersion into MB; adjacent control 2 tissue (n = 10) was immersed in MB without ultrasound exposure. The MB content was higher (p < 0.05) in HIFU-treated samples all the way to a depth of 600 µm from AC surface when compared to controls. Chondrocyte viability and RNA expression levels associated with cartilage degeneration were not different in HIFU-treated samples when compared to controls (p > 0.05). To conclude, HIFU delivers molecules into articular cartilage without major short-term concerns about safety. The method is a candidate for a future approach for managing OA.
Novel sustainable biobased flame retardant from functionalized vegetable oil for enhanced flame retardancy of engineering plastic
Authors: Chang Boon Peng , Thakur Suman , Mohanty Amar K. , Misra Manjusri 
Published: November 2019

AbstractThe flame retardancy of an engineering plastic, poly(butylene terephthalate) (PBT), with a biobased flame retardant (FR) made from phosphorylated linseed oil (PLO) and phosphorylated downstream corn oil (PCO) was studied. Different phosphorus moieties were incorporated into the vegetable oil backbone through a ring-opening reaction. The chemical structure of the phosphorylated oil was confirmed by Fourier-transform infrared (FTIR) and nuclear resonance magnetic (NMR) spectroscopy. It was found that the incorporation of only 7.5 wt% of PLO was sufficient to change the UL-94 fire class of PBT from non-rating to V-0. The flame-retardancy mechanism of the PBT/PLO blends was evaluated from TGA-FTIR analysis. The combined effects of the gas phase mechanism and the dripping tendency of the blends aided to retard the flame propagation effectively. As the synthesized PLO and PCO contained high free fatty acids, the acid-ester exchange reaction occurred in the blends to form oligomers during the ignition. As a result, the blend dripped immediately and the drips carried all the heat to prevent fire. This work suggests that this sustainable biobased FR could be a desirable alternative to halogen-based FRs for PBT and other engineering polymers to develop more environmentally friendly FR products for various future applications.
An Exploratory Study of Predictors of Response to Vagus Nerve Stimulation Paired with Upper-Limb Rehabilitation After Ischemic Stroke
Authors: Dickie David Alexander , Kimberley Teresa Jacobson , Pierce David , Engineer Navzer , Tarver W. Brent , Dawson Jesse 
Published: November 2019

AbstractWe have previously shown the safety and feasibility of vagus nerve stimulation (VNS) paired with upper-limb rehabilitation after ischemic stroke. In this exploratory study, we assessed whether clinical and brain MRI variables predict response to treatment. We used data from two completed randomised and blinded clinical trials (N = 35). All participants had moderate to severe upper-limb weakness and were randomised to 6-weeks intensive physiotherapy with or without VNS. Participants had 3 T brain MRI at baseline. The primary outcome was change in Fugl-Meyer Assessment, upper-extremity score (FMA-UE) from baseline to the first day after therapy completion. We used general linear regression to identify clinical and brain MRI predictors of change in FMA-UE. VNS-treated participants had greater improvement in FMA-UE at day-1 post therapy than controls (8.63 ± 5.02 versus 3.79 ± 5.04 points, t = 2.83, Cohen’s d = 0.96, P = 0.008). Higher cerebrospinal fluid volume was associated with less improvement in FMA-UE in the control but not VNS group. This was also true for white matter hyperintensity volume but not after removal of an outlying participant from the control group. Responders in the VNS group had more severe arm impairment at baseline than responders to control. A phase III trial is now underway to formally determine whether VNS improves outcomes and will explore whether these differ in people with more severe baseline upper-limb disability and cerebrovascular disease.
Network-based Biased Tree Ensembles (NetBiTE) for Drug Sensitivity Prediction and Drug Sensitivity Biomarker Identification in Cancer
Authors: Oskooei Ali , Manica Matteo , Mathis Roland , Martínez María Rodríguez 
Published: November 2019

AbstractWe present the Network-based Biased Tree Ensembles (NetBiTE) method for drug sensitivity prediction and drug sensitivity biomarker identification in cancer using a combination of prior knowledge and gene expression data. Our devised method consists of a biased tree ensemble that is built according to a probabilistic bias weight distribution. The bias weight distribution is obtained from the assignment of high weights to the drug targets and propagating the assigned weights over a protein-protein interaction network such as STRING. The propagation of weights, defines neighborhoods of influence around the drug targets and as such simulates the spread of perturbations within the cell, following drug administration. Using a synthetic dataset, we showcase how application of biased tree ensembles (BiTE) results in significant accuracy gains at a much lower computational cost compared to the unbiased random forests (RF) algorithm. We then apply NetBiTE to the Genomics of Drug Sensitivity in Cancer (GDSC) dataset and demonstrate that NetBiTE outperforms RF in predicting IC50 drug sensitivity, only for drugs that target membrane receptor pathways (MRPs): RTK, EGFR and IGFR signaling pathways. We propose based on the NetBiTE results, that for drugs that inhibit MRPs, the expression of target genes prior to drug administration is a biomarker for IC50 drug sensitivity following drug administration. We further verify and reinforce this proposition through control studies on, PI3K/MTOR signaling pathway inhibitors, a drug category that does not target MRPs, and through assignment of dummy targets to MRP inhibiting drugs and investigating the variation in NetBiTE accuracy.
Correlated impurity complex in the asymmetric tunneling contact: an ideal system to observe negative tunneling conductivity
Authors: Maslova N. S. , Arseyev P. I. , Mantsevich V. N. 
Published: November 2019

AbstractWe studied theoretically electron transport through the impurity complex localized between the tunneling contact leads by means of the generalized Keldysh diagram technique. The formation of multiple well pronounced regions with negative tunneling conductivity in the I-V characteristics was revealed. The appearance of negative tunneling conductivity is caused by the presence of both strong Coulomb correlations and the asymmetry of tunneling rates, which lead to the blockade of the electron transport through the system for a certain values of applied bias. The developed theory and obtained results may be useful for the application of impurity (dopant) atoms as a basic elements in modern nanoelectronic circuits.
A sensitive fluorescence-based assay to monitor enzymatic activity of the essential integral membrane protein Apolipoprotein N-acyltransferase (Lnt)
Authors: Nozeret Karine , Boucharlat Alix , Agou Fabrice , Buddelmeijer Nienke 
Published: November 2019

AbstractLipoprotein modification is an essential process in Gram-negative bacteria. The action of three integral membrane proteins that catalyze the transfer of fatty acids derived from membrane phospholipids or cleave the signal peptide of the lipoprotein substrate result in the formation of mature triacylated proteins. Inactivation of the enzymes leads to mis-localization of immature lipoproteins and consequently cell death. Biochemical studies and the development of in vitro assays are challenging due to the fact that the enzymes and substrates are all membrane-embedded proteins difficult to overproduce and purify. Here we describe a sensitive fluorescence-based assay to monitor bacterial apolipoprotein N-acyltransferase activity.
α-Synuclein oligomers mediate the aberrant form of spike-induced calcium release from IP3 receptor
Authors: Yamamoto Kenji , Izumi Yasuhiko , Arifuku Monami , Kume Toshiaki , Sawada Hideyuki 
Published: November 2019

AbstractEmerging evidence implicates α-synuclein oligomers as potential culprits in the pathogenesis of Lewy body disease (LBD). Soluble oligomeric α-synuclein accumulation in cytoplasm is believed to modify neuronal activities and intraneural Ca2+dynamics, which augment the metabolic burden in central neurons vulnerable to LBD, although this hypothesis remains to be fully tested. We evaluated how intracellular α-synuclein oligomers affect the neuronal excitabilities and Ca2+dynamics of pyramidal neurons in neocortical slices from mice. Intracellular application of α-synuclein containing stable higher-order oligomers (αSNo) significantly reduced spike frequency during current injection, elongated the duration of spike afterhyperpolarization (AHP), and enlarged AHP current charge in comparison with that of α-synuclein without higher-order oligomers. This αSNo-mediated alteration was triggered by spike-induced Ca2+release from inositol trisphosphate receptors (IP3R) functionally coupled with L-type Ca2+channels and SK-type K+channels. Further electrophysiological and immunochemical observations revealed that α-synuclein oligomers greater than 100 kDa were directly associated with calcium-binding protein 1, which is responsible for regulating IP3R gating. They also block Ca2+-dependent inactivation of IP3R, and trigger Ca2+-induced Ca2+release from IP3R during multiple spikes. This aberrant machinery may result in intraneural Ca2+dyshomeostasis and may be the molecular basis for the vulnerability of neurons in LBD brains.
Satellite Laser-Ranging as a Probe of Fundamental Physics
Authors: Ciufolini Ignazio , Matzner Richard , Paolozzi Antonio , Pavlis Erricos C. , Sindoni Giampiero , Ries John , Gurzadyan Vahe , Koenig Rolf 
Published: November 2019

AbstractSatellite laser-ranging is successfully used in space geodesy, geodynamics and Earth sciences; and to test fundamental physics and specific features of General Relativity. We present a confirmation to approximately one part in a billion of the fundamental weak equivalence principle (“uniqueness of free fall”) in the Earth’s gravitational field, obtained with three laser-ranged satellites, at previously untested range and with previously untested materials. The weak equivalence principle is at the foundation of General Relativity and of most gravitational theories.