bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial complex I inhibition triggers a mitophagy-dependent ROS increase leading to necroptosis and ferroptosis in melanoma cells
Authors: Basit Farhan , van Oppen Lisanne MPE , Schöckel Laura , Bossenbroek Hasse M , van Emst-de Vries Sjenet E , Hermeling Johannes CW , Grefte Sander , Kopitz Charlotte , Heroult Melanie , HGM Willems Peter , Koopman Werner JH 
Published: March 2017

AbstractInhibition of complex I (CI) of the mitochondrial respiratory chain by BAY 87-2243 (‘BAY’) triggers death of BRAFV600E melanoma cell lines and inhibits in vivo tumor growth. Here we studied the mechanism by which this inhibition induces melanoma cell death. BAY treatment depolarized the mitochondrial membrane potential (Δψ), increased cellular ROS levels, stimulated lipid peroxidation and reduced glutathione levels. These effects were paralleled by increased opening of the mitochondrial permeability transition pore (mPTP) and stimulation of autophagosome formation and mitophagy. BAY-induced cell death was not due to glucose shortage and inhibited by the antioxidant α-tocopherol and the mPTP inhibitor cyclosporin A. Tumor necrosis factor receptor-associated protein 1 (TRAP1) overexpression in BAY-treated cells lowered ROS levels and inhibited mPTP opening and cell death, whereas the latter was potentiated by TRAP1 knockdown. Knockdown of autophagy-related 5 (ATG5) inhibited the BAY-stimulated autophagosome formation, cellular ROS increase and cell death. Knockdown of phosphatase and tensin homolog-induced putative kinase 1 (PINK1) inhibited the BAY-induced Δψ depolarization, mitophagy stimulation, ROS increase and cell death. Dynamin-related protein 1 (Drp1) knockdown induced mitochondrial filamentation and inhibited BAY-induced cell death. The latter was insensitive to the pancaspase inhibitor z-VAD-FMK, but reduced by necroptosis inhibitors (necrostatin-1, necrostatin-1s)) and knockdown of key necroptosis proteins (receptor-interacting serine/threonine-protein kinase 1 (RIPK1) and mixed lineage kinase domain-like (MLKL)). BAY-induced cell death was also reduced by the ferroptosis inhibitor ferrostatin-1 and overexpression of the ferroptosis-inhibiting protein glutathione peroxidase 4 (GPX4). This overexpression also inhibited the BAY-induced ROS increase and lipid peroxidation. Conversely, GPX4 knockdown potentiated BAY-induced cell death. We propose a chain of events in which: (i) CI inhibition induces mPTP opening and Δψ depolarization, that (ii) stimulate autophagosome formation, mitophagy and an associated ROS increase, leading to (iii) activation of combined necroptotic/ferroptotic cell death.
FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons
Authors: Errichelli Lorenzo , Dini Modigliani Stefano , Laneve Pietro , Colantoni Alessio , Legnini Ivano , Capauto Davide , Rosa Alessandro , De Santis Riccardo , Scarfò Rebecca , Peruzzi Giovanna , Lu Lei , Caffarelli Elisa , Shneider Neil A. , Morlando Mariangela , Bozzoni Irene 
Published: March 2017

AbstractThe RNA-binding protein FUS participates in several RNA biosynthetic processes and has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Here we report that FUS controls back-splicing reactions leading to circular RNA (circRNA) production. We identified circRNAs expressed in in vitro-derived mouse motor neurons (MNs) and determined that the production of a considerable number of these circRNAs is regulated by FUS. Using RNAi and overexpression of wild-type and ALS-associated FUS mutants, we directly correlate the modulation of circRNA biogenesis with alteration of FUS nuclear levels and with putative toxic gain of function activities. We also demonstrate that FUS regulates circRNA biogenesis by binding the introns flanking the back-splicing junctions and that this control can be reproduced with artificial constructs. Most circRNAs are conserved in humans and specific ones are deregulated in human-induced pluripotent stem cell-derived MNs carrying the FUSP525L mutation associated with ALS.
Epithelial tension in the second heart field promotes mouse heart tube elongation
Authors: Francou Alexandre , De Bono Christopher , Kelly Robert G. 
Published: March 2017

AbstractExtension of the vertebrate heart tube is driven by progressive addition of second heart field (SHF) progenitor cells to the poles of the heart. Defects in this process cause a spectrum of congenital anomalies. SHF cells form an epithelial layer in splanchnic mesoderm in the dorsal wall of the pericardial cavity. Here we report oriented cell elongation, polarized actomyosin distribution and nuclear YAP/TAZ in a proliferative centre in the posterior dorsal pericardial wall during heart tube extension. These parameters are indicative of mechanical stress, further supported by analysis of cell shape changes in wound assays. Time course and mutant analysis identifies SHF deployment as a source of epithelial tension. Moreover, cell division and oriented growth in the dorsal pericardial wall align with the axis of cell elongation, suggesting that epithelial tension in turn contributes to heart tube extension. Our results implicate tissue-level forces in the regulation of heart tube extension.
Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy
Authors: Afshari Natalie A. , Igo Robert P. , Morris Nathan J. , Stambolian Dwight , Sharma Shiwani , Pulagam V. Lakshmi , Dunn Steven , Stamler John F. , Truitt Barbara J. , Rimmler Jacqueline , Kuot Abraham , Croasdale Christopher R. , Qin Xuejun , Burdon Kathryn P. , Riazuddin S. Amer , Mills Richard , Klebe Sonja , Minear Mollie A. , Zhao Jiagang , Balajonda Elmer , Rosenwasser George O. , Baratz Keith H , Mootha V. Vinod , Patel Sanjay V. , Gregory Simon G. , Bailey-Wilson Joan E. , Price Marianne O. , Price Francis W. , Craig Jamie E. , Fingert John H. , Gottsch John D. , Aldave Anthony J. , Klintworth Gordon K. , Lass Jonathan H. , Li Yi-Ju , Iyengar Sudha K. 
Published: March 2017

AbstractThe structure of the cornea is vital to its transparency, and dystrophies that disrupt corneal organization are highly heritable. To understand the genetic aetiology of Fuchs endothelial corneal dystrophy (FECD), the most prevalent corneal disorder requiring transplantation, we conducted a genome-wide association study (GWAS) on 1,404 FECD cases and 2,564 controls of European ancestry, followed by replication and meta-analysis, for a total of 2,075 cases and 3,342 controls. We identify three novel loci meeting genome-wide significance (P<5 × 10−8): KANK4 rs79742895, LAMC1 rs3768617 and LINC00970/ATP1B1 rs1200114. We also observe an overwhelming effect of the established TCF4 locus. Interestingly, we detect differential sex-specific association at LAMC1, with greater risk in women, and TCF4, with greater risk in men. Combining GWAS results with biological evidence we expand the knowledge of common FECD loci from one to four, and provide a deeper understanding of the underlying pathogenic basis of FECD.
An Improved Racetrack Structure for Transporting a Skyrmion
Authors: Lai P. , Zhao G. P. , Tang H. , Ran N. , Wu S. Q. , Xia J. , Zhang X. , Zhou Y. 
Published: March 2017

AbstractMagnetic skyrmions are promising building blocks for next generation data storage due to their stability, small size and extremely low currents to drive them, which can be used instead of traditional magnetic domain walls to store information as data bits in metalic racetrack memories. However, skyrmions can drift from the direction of electron flow due to the Magnus force and thus may annihilate at the racetrack edges, resulting in the loss of information. Here we propose a new skyrmion-based racetrack structure by adding high-K materials (materials with high magnetic crystalline anisotropy) at the edges, which confines the skyrmions in the center region of the metalic racetrack efficiently. This design can overcome both the clogging and annihilation of skyrmions according to our micromagnetic simulation, which occur normally for skyrmions moving on a racetrack under small and large driving currents, respectively. Phase diagrams for skyrmion motion on the proposed racetrack with various values of current density and racetrack edge width have been calculated and given, showing that skyrmions can be driven at a high speed (about 300 m/s) in the racetrack under relatively smaller driving currents. This design offers the possiblity of building an ultrafast and energy-efficient skyrmion transport device.
STITCHER 2.0: primer design for overlapping PCR applications
Authors: O’Halloran Damien M. , Uriagereka-Herburger Isabel , Bode Katrin 
Published: March 2017

AbstractOverlapping polymerase chain reaction (PCR) is a common technique used by researchers in very diverse fields that enables the user to ‘stitch’ individual pieces of DNA together. Previously, we have reported a web based tool called STITCHER that provides a platform for researchers to automate the design of primers for overlapping PCR applications. Here we present STITCHER 2.0, which represents a substantial update to STITCHER. STITCHER 2.0 is a newly designed web tool that automates the design of primers for overlapping PCR. Unlike STITCHER, STITCHER 2.0 considers diverse algorithmic parameters, and returns multiple result files that include a facility for the user to draw their own primers as well as comprehensive visual guides to the user’s input, output, and designed primers. These result files provide greater control and insight during experimental design and troubleshooting. STITCHER 2.0 is freely available to all users without signup or login requirements and can be accessed at the following webpage: www.ohalloranlab.net/STITCHER2.html.
SGK1 affects RAN/RANBP1/RANGAP1 via SP1 to play a critical role in pre-miRNA nuclear export: a new route of epigenomic regulation
Authors: Dattilo Vincenzo , D’Antona Lucia , Talarico Cristina , Capula Mjriam , Catalogna Giada , Iuliano Rodolfo , Schenone Silvia , Roperto Sante , Bianco Cataldo , Perrotti Nicola , Amato Rosario 
Published: March 2017

AbstractThe serum- and glucocorticoid-regulated kinase (SGK1) controls cell transformation and tumor progression. SGK1 affects mitotic stability by regulating the expression of RANBP1/RAN. Here, we demonstrate that SGK1 fluctuations indirectly modify the maturation of pre-miRNAs, by modulating the equilibrium of the RAN/RANBP1/RANGAP1 axis, the main regulator of nucleo-cytoplasmic transport. The levels of pre-miRNAs and mature miRNAs were assessed by qRT-PCR, in total extracts and after differential nuclear/cytoplasmic extraction. RANBP1 expression is the limiting step in the regulation of SGK1-SP1 dependent nuclear export. These results were validated in unrelated tumor models and primary human fibroblasts and corroborated in tumor-engrafted nude mice. The levels of pri-miRNAs, DROSHA, DICER and the compartmental distribution of XPO5 were documented. Experiments using RANGTP conformational antibodies confirmed that SGK1, through RANBP1, decreases the level of the GTP-bound state of RAN. This novel mechanism may play a role in the epigenomic regulation of cell physiology and fate.
Work Function Tuning in Two-Dimensional MoS2 Field-Effect-Transistors with Graphene and Titanium Source-Drain Contacts
Authors: Baik Seung Su , Im Seongil , Choi Hyoung Joon 
Published: March 2017

AbstractBased on the first principles calculation, we investigate the electronic band structures of graphene-MoS2and Ti-MoS2heterojunctions under gate-voltages. By simultaneous control of external electric fields and carrier charging concentrations, we show that the graphene’s Dirac point position inside the MoS2bandgap is easily modulated with respect to the co-varying Fermi level, while keeping the graphene’s linear band structure around the Dirac point. The easy modulation of graphene bands is not confined to the special cases where the conduction-band-minimum point of MoS2and the Dirac point of graphene are matched up in reciprocal space, but is generalized to their dislocated cases. This flexibility caused by the strong decoupling between graphene and MoS2bands enhances the gate-controlled switching performance in MoS2-graphene hybrid stacking-device.
Integrating Sequence-based GWAS and RNA-Seq Provides Novel Insights into the Genetic Basis of Mastitis and Milk Production in Dairy Cattle
Authors: Fang Lingzhao , Sahana Goutam , Su Guosheng , Yu Ying , Zhang Shengli , Lund Mogens Sandø , Sørensen Peter 
Published: March 2017

AbstractConnecting genome-wide association study (GWAS) to biological mechanisms underlying complex traits is a major challenge. Mastitis resistance and milk production are complex traits of economic importance in the dairy sector and are associated with intra-mammary infection (IMI). Here, we integrated IMI-relevant RNA-Seq data from Holstein cattle and sequence-based GWAS data from three dairy cattle breeds (i.e., Holstein, Nordic red cattle, and Jersey) to explore the genetic basis of mastitis resistance and milk production using post-GWAS analyses and a genomic feature linear mixed model. At 24 h post-IMI, genes responsive to IMI in the mammary gland were preferentially enriched for genetic variants associated with mastitis resistance rather than milk production. Response genes in the liver were mainly enriched for variants associated with mastitis resistance at an early time point (3 h) post-IMI, whereas responsive genes at later stages were enriched for associated variants with milk production. The up- and down-regulated genes were enriched for associated variants with mastitis resistance and milk production, respectively. The patterns were consistent across breeds, indicating that different breeds shared similarities in the genetic basis of these traits. Our approaches provide a framework for integrating multiple layers of data to understand the genetic architecture underlying complex traits.
Excitonic structure and pumping power dependent emission blue-shift of type-II quantum dots
Authors: Klenovský Petr , Steindl Petr , Geffroy Dominique 
Published: March 2017

AbstractIn this work we study theoretically and experimentally the multi-particle structure of the so-called type-II quantum dots with spatially separated electrons and holes. Our calculations based on customarily developed full configuration interaction ap- proach reveal that exciton complexes containing holes interacting with two or more electrons exhibit fairly large antibinding energies. This effect is found to be the hallmark of the type-II confinement. In addition, an approximate self-consistent solution of the multi-exciton problem allows us to explain two pronounced phenomena: the blue-shift of the emission with pumping and the large inhomogeneous spectral broadening, both of those eluding explanation so far. The results are confirmed by detailed intensity and polarization resolved photoluminescence measurements on a number of type-II samples.
Novel conjugates of aminoadamantanes with carbazole derivatives as potential multitarget agents for AD treatment
Authors: Bachurin Sergey O. , Shevtsova Elena F. , Makhaeva Galina F. , Grigoriev Vladimir V. , Boltneva Natalia P. , Kovaleva Nadezhda V. , Lushchekina Sofya V. , Shevtsov Pavel N. , Neganova Margarita E. , Redkozubova Olga M. , Bovina Elena V. , Gabrelyan Alexey V. , Fisenko Vladimir P. , Sokolov Vladimir B. , Aksinenko Alexey Yu , Echeverria Valentina , Barreto George E. , Aliev Gjumrakch 
Published: March 2017

AbstractA new group of compounds, promising for the design of original multitarget therapeutic agents for treating neurodegenerative diseases, based on conjugates of aminoadamantane and carbazole derivatives was synthesized and investigated. Compounds of these series were found to interact with a group of targets that play an important role in the development of this type of diseases. First of all, these compounds selectively inhibit butyrylcholinesterase, block NMDA receptors containing NR2B subunits while maintaining the properties of MK-801 binding site blockers, exert microtubules stabilizing properties, and possess the ability to protect nerve cells from death at the calcium overload conditions. The leading compound C-2h has been shown the most promising effects on all analyzed parameters. Thus, these compounds can be regarded as promising candidates for the design of multi-target disease-modifying drugs for treatment of AD and/or similar neuropathologies.
Azole-resistant Aspergillus fumigatus harboring TR34/L98H, TR46/Y121F/T289A and TR53 mutations related to flower fields in Colombia
Authors: Alvarez-Moreno Carlos , Lavergne Rose-Anne , Hagen Ferry , Morio Florent , Meis Jacques F. , Le Pape Patrice 
Published: March 2017

AbstractResistance to triazoles in Aspergillus fumigatus has been reported in azole-naive patients in Europe, Asia, Australia and North America. This resistance has been linked to fungicide-driven mutations in the cyp51A gene and its promoter region. We investigated the presence of environmental azole-resistant A. fumigatus strains related to the use of azole fungicides in Colombia. Soil samples were collected from flower beds, flower fields and public gardens from the outskirts, suburbs and city centre of Bogotá. Out of the 86 soil samples taken, 17 (19.8%) grew A. fumigatus of whom eight (9.3%) contained 40 strains able to grow on azole-containing itraconazole and/or voriconazole supplemented media. All but one triazole-resistant strains were isolated from soil samples collected from flower fields and flower beds (39/40). Importantly, the majority had the TR46/Y121F/T289A, TR34/L98H, and TR53 molecular resistance mechanisms and one azole resistant strain had a wild-type cyp51A gene. Soil samples from flower fields and beds contained 4 azole fungicides (penconazole, difenoconazole, tetraconazole and tebuconazole) above the limit of detection. Our findings underline the need for extensive investigations to determine azole-resistant A. fumigatus prevalence in both clinical and environmental samples in other regions of Latin America.
Quantitative analysis of molecular partition towards lipid membranes using surface plasmon resonance
Authors: Figueira Tiago N. , Freire João M. , Cunha-Santos Catarina , Heras Montserrat , Gonçalves João , Moscona Anne , Porotto Matteo , Salomé Veiga Ana , Castanho Miguel A. R. B. 
Published: March 2017

AbstractUnderstanding the interplay between molecules and lipid membranes is fundamental when studying cellular and biotechnological phenomena. Partition between aqueous media and lipid membranes is key to the mechanism of action of many biomolecules and drugs. Quantifying membrane partition, through adequate and robust parameters, is thus essential. Surface Plasmon Resonance (SPR) is a powerful technique for studying 1:1 stoichiometric interactions but has limited application to lipid membrane partition data. We have developed and applied a novel mathematical model for SPR data treatment that enables determination of kinetic and equilibrium partition constants. The method uses two complementary fitting models for association and dissociation sensorgram data. The SPR partition data obtained for the antibody fragment F63, the HIV fusion inhibitor enfuvirtide, and the endogenous drug kyotorphin towards POPC membranes were compared against data from independent techniques. The comprehensive kinetic and partition models were applied to the membrane interaction data of HRC4, a measles virus entry inhibitor peptide, revealing its increased affinity for, and retention in, cholesterol-rich membranes. Overall, our work extends the application of SPR beyond the realm of 1:1 stoichiometric ligand-receptor binding into a new and immense field of applications: the interaction of solutes such as biomolecules and drugs with lipids.
Cultivar-specific gene modulation in Vitis vinifera: analysis of the promoters regulating the expression of WOX transcription factors
Authors: Boccacci Paolo , Mela Anita , Pavez Mina Catalina , Chitarra Walter , Perrone Irene , Gribaudo Ivana , Gambino Giorgio 
Published: March 2017

AbstractThe family of Wuschel-related Homeobox (WOX) genes is a class of transcription factors involved in the early stages of embryogenesis and organ development in plants. Some of these genes have shown different transcription levels in embryogenic tissues and mature organs in two different cultivars of Vitis vinifera: ‘Chardonnay’ (CH) and ‘Cabernet Sauvignon’ (CS). Therefore, we investigated the genetic basis responsible for these differences by cloning and sequencing in both the cultivars the promoter regions (~2000 bp) proximal to the transcription start site of five VvWOX genes. We then introduced these promoters into Arabidopsis thaliana for expression pattern characterisation using the GUS reporter gene. In the transgenic Arabidopsis, two promoters isolated from CS (pVvWOX13C_CS and pVvWOX6_CS) induced increased expression compared to the sequence isolated in CH, confirming the data obtained in grapevine tissues. These results were corroborated by transient expression assays using the agroinfiltration approach in grapevine somatic embryos. Truncated versions of pVvWOX13C demonstrated that few nucleotide differences between the sequences isolated from CH and CS are pivotal for the transcriptional regulation of VvWOX13C. Analysis of promoters using heterologous and homologous systems appear to be effective for exploring gene modulation linked with intervarietal sequence variation in grapevine.
Identifying large-scale patterns of unpredictability and response to insolation in atmospheric data
Authors: Arizmendi Fernando , Barreiro Marcelo , Masoller Cristina 
Published: March 2017

AbstractUnderstanding the complex dynamics of the atmosphere is of paramount interest due to its impact in the entire climate system and in human society. Here we focus on identifying, from data, the geographical regions which have similar atmospheric properties. We study surface air temperature (SAT) time series with monthly resolution, recorded at a regular grid covering the Earth surface. We consider two datasets: NCEP CDAS1 and ERA Interim reanalysis. We show that two surprisingly simple measures are able to extract meaningful information: i) the distance between the lagged SAT and the incoming solar radiation and ii) the Shannon entropy of SAT and SAT anomalies. The distance uncovers well-defined spatial patterns formed by regions with similar SAT response to solar forcing while the entropy uncovers regions with similar degree of SAT unpredictability. The entropy analysis also allows identifying regions in which SAT has extreme values. Importantly, we uncover differences between the two datasets which are due to the presence of extreme values in one dataset but not in the other. Our results indicate that the distance and entropy measures can be valuable tools for the study of other climatological variables, for anomaly detection and for performing model inter-comparisons.
Removal of Cr(VI) from solution by free and immobilised spores of Aspergillus niger
Authors: Ren Binqiao , Wang Jingyao , Zhang Weijun , Kan Kan , Zhao Luyang , Song Xiaoxiao , Cui Chongwei 
Published: March 2017

Despite the current interest in microbial methods for the detoxification of effluents, relatively little work has focused on the characterisation of metal uptake by small Aspergillus niger spores, particularly for heavy metals present at different and low concentrations. The objective of this study was to determine the ability of A. niger spores (free spores and as immobilised biosorbent) to remove toxic metals from an industrial wastewater as a batch system. The simultaneous influences of the mass of pH and biomass on the ability of spores to uptake of Cr(VI) were analysed. The free and immobilised biosorbent removed Cr(VI) efficiently with a maximum metal removal capacity of 55 and 40 mg/g, respectively. The biosorption mechanism was also investigated using Fourier transfer infrared and scanning electron microscopy. Immobilised spores of A. niger were more stable in solutions at different pH levels and allowed easier separation from aqueous solution than free spores, suggesting significant potential for future industrial application.