bluuebunny/crossref_metadata_2025_split huggingface dataset:
microRNA-378a-5p iS a novel positive regulator of melanoma progression
Authors: Tupone Maria Grazia , D’Aguanno Simona , Di Martile Marta , Valentini Elisabetta , Desideri Marianna , Trisciuoglio Daniela , Donzelli Sara , Sacconi Andrea , Buglioni Simonetta , Ercolani Cristiana , Biagioni Alessio , Fibbi Gabriella , Fattore Luigi , Mancini Rita , Ciliberto Gennaro , Blandino Giovanni , Del Bufalo Donatella 
Published: February 2020

AbstractEvaluating the expression levels of miR-378a-5p both in a large melanoma patient cohort from The Cancer Genome Atlas database and in melanoma patients from our Institute, we found that miR-378a-5p is upregulated in metastatic melanoma specimens. miR-378a-5p expression was also increased in melanoma cells resistant to target therapy, and decreased in response to drug treatment. We also demonstrated that overexpression of miR-378a-5p enhances in vitro cell invasion and migration, and facilitates the ability of melanoma cells to form de novo vasculogenic structures. While performing downstream targeting studies, we confirmed the ability of miR-378a-5p to modulate the expression of known target genes, such as SUFU, FUS-1, and KLF9. Luciferase-3′UTR experiments also identified STAMBP and HOXD10 as new miR-378a-5p target genes. MMP2 and uPAR, two HOXD10 target genes, were positively regulated by miR-378a-5p. Genetic and pharmacologic approaches inhibiting uPAR expression and activity evidenced that the in vitro tumor-promoting functions of miR-378a-5p, were in part mediated by uPAR. Of note miR-378a-5p was also able to increase VEGF, as well as in vitro and in vivo angiogenesis. Finally, genetic and pharmacologic modulation of Bcl-2 evidenced Bcl-2 ability to regulate miR-378a-5p expression. In conclusion, to the best of our knowledge, this is the first study demonstrating that miR-378a-5p acts as an oncogenic microRNA in melanoma.
Liquids relax and unify strain in graphene
Authors: Belyaeva Liubov A. , Jiang Lin , Soleimani Alireza , Methorst Jeroen , Risselada H. Jelger , Schneider Grégory F. 
Published: February 2020

AbstractSolid substrates often induce non-uniform strain and doping in graphene monolayer, therefore altering the intrinsic properties of graphene, reducing its charge carrier mobilities and, consequently, the overall electrical performance. Here, we exploit confocal Raman spectroscopy to study graphene directly free-floating on the surface of water, and show that liquid supports relief the preexisting strain, have negligible doping effect and restore the uniformity of the properties throughout the graphene sheet. Such an effect originates from the structural adaptability and flexibility, lesser contamination and weaker intermolecular bonding of liquids compared to solid supports, independently of the chemical nature of the liquid. Moreover, we demonstrate that water provides a platform to study and distinguish chemical defects from substrate-induced defects, in the particular case of hydrogenated graphene. Liquid supports, thus, are advantageous over solid supports for a range of applications, particularly for monitoring changes in the graphene structure upon chemical modification.
Endogenous topoisomerase II-mediated DNA breaks drive thymic cancer predisposition linked to ATM deficiency
Authors: Álvarez-Quilón Alejandro , Terrón-Bautista José , Delgado-Sainz Irene , Serrano-Benítez Almudena , Romero-Granados Rocío , Martínez-García Pedro Manuel , Jimeno-González Silvia , Bernal-Lozano Cristina , Quintero Cristina , García-Quintanilla Lourdes , Cortés-Ledesma Felipe 
Published: February 2020

AbstractThe ATM kinase is a master regulator of the DNA damage response to double-strand breaks (DSBs) and a well-established tumour suppressor whose loss is the cause of the neurodegenerative and cancer-prone syndrome Ataxia-Telangiectasia (A-T). A-T patients and Atm−/− mouse models are particularly predisposed to develop lymphoid cancers derived from deficient repair of RAG-induced DSBs during V(D)J recombination. Here, we unexpectedly find that specifically disturbing the repair of DSBs produced by DNA topoisomerase II (TOP2) by genetically removing the highly specialised repair enzyme TDP2 increases the incidence of thymic tumours in Atm−/− mice. Furthermore, we find that TOP2 strongly colocalizes with RAG, both genome-wide and at V(D)J recombination sites, resulting in an increased endogenous chromosomal fragility of these regions. Thus, our findings demonstrate a strong causal relationship between endogenous TOP2-induced DSBs and cancer development, confirming these lesions as major drivers of ATM-deficient lymphoid malignancies, and potentially other conditions and cancer types.
Glass transition temperature from the chemical structure of conjugated polymers
Authors: Xie Renxuan , Weisen Albree R. , Lee Youngmin , Aplan Melissa A. , Fenton Abigail M. , Masucci Ashley E. , Kempe Fabian , Sommer Michael , Pester Christian W. , Colby Ralph H. , Gomez Enrique D. 
Published: February 2020

AbstractThe glass transition temperature (Tg) is a key property that dictates the applicability of conjugated polymers. TheTgdemarks the transition into a brittle glassy state, making its accurate prediction for conjugated polymers crucial for the design of soft, stretchable, or flexible electronics. Here we show that a single adjustable parameter can be used to build a relationship between theTgand the molecular structure of 32 semiflexible (mostly conjugated) polymers that differ drastically in aromatic backbone and alkyl side chain chemistry. An effective mobility value,ζ, is calculated using an assigned atomic mobility value within each repeat unit. The only adjustable parameter in the calculation ofζis the ratio of mobility between conjugated and non-conjugated atoms. We show thatζcorrelates strongly to theTg, and that this simple method predicts theTgwith a root-mean-square error of 13 °C for conjugated polymers with alkyl side chains.
MYCN amplification and ATRX mutations are incompatible in neuroblastoma
Authors: Zeineldin Maged , Federico Sara , Chen Xiang , Fan Yiping , Xu Beisi , Stewart Elizabeth , Zhou Xin , Jeon Jongrye , Griffiths Lyra , Nguyen Rosa , Norrie Jackie , Easton John , Mulder Heather , Yergeau Donald , Liu Yanling , Wu Jianrong , Van Ryn Collin , Naranjo Arlene , Hogarty Michael D. , Kamiński Marcin M. , Valentine Marc , Pruett-Miller Shondra M. , Pappo Alberto , Zhang Jinghui , Clay Michael R. , Bahrami Armita , Vogel Peter , Lee Seungjae , Shelat Anang , Sarthy Jay F. , Meers Michael P. , George Rani E. , Mardis Elaine R. , Wilson Richard K. , Henikoff Steven , Downing James R. , Dyer Michael A. 
Published: February 2020

AbstractAggressive cancers often have activating mutations in growth-controlling oncogenes and inactivating mutations in tumor-suppressor genes. In neuroblastoma, amplification of the MYCN oncogene and inactivation of the ATRX tumor-suppressor gene correlate with high-risk disease and poor prognosis. Here we show that ATRX mutations and MYCN amplification are mutually exclusive across all ages and stages in neuroblastoma. Using human cell lines and mouse models, we found that elevated MYCN expression and ATRX mutations are incompatible. Elevated MYCN levels promote metabolic reprogramming, mitochondrial dysfunction, reactive-oxygen species generation, and DNA-replicative stress. The combination of replicative stress caused by defects in the ATRX–histone chaperone complex, and that induced by MYCN-mediated metabolic reprogramming, leads to synthetic lethality. Therefore, ATRX and MYCN represent an unusual example, where inactivation of a tumor-suppressor gene and activation of an oncogene are incompatible. This synthetic lethality may eventually be exploited to improve outcomes for patients with high-risk neuroblastoma.
A square-root topological insulator with non-quantized indices realized with photonic Aharonov-Bohm cages
Authors: Kremer Mark , Petrides Ioannis , Meyer Eric , Heinrich Matthias , Zilberberg Oded , Szameit Alexander 
Published: February 2020

AbstractTopological Insulators are a novel state of matter where spectral bands are characterized by quantized topological invariants. This unique quantized nonlocal property commonly manifests through exotic bulk phenomena and corresponding robust boundary effects. In our work we study a system where the spectral bands are associated with non-quantized indices, but nevertheless possess robust boundary states. We present a theoretical analysis, where we show that the square of the Hamiltonian exhibits quantized indices. The findings are experimentally demonstrated by using photonic Aharonov-Bohm cages.
Tracking attosecond electronic coherences using phase-manipulated extreme ultraviolet pulses
Authors: Wituschek Andreas , Bruder Lukas , Allaria Enrico , Bangert Ulrich , Binz Marcel , Borghes Roberto , Callegari Carlo , Cerullo Giulio , Cinquegrana Paolo , Giannessi Luca , Danailov Miltcho , Demidovich Alexander , Di Fraia Michele , Drabbels Marcel , Feifel Raimund , Laarmann Tim , Michiels Rupert , Mirian Najmeh Sadat , Mudrich Marcel , Nikolov Ivaylo , O’Shea Finn H. , Penco Giuseppe , Piseri Paolo , Plekan Oksana , Prince Kevin Charles , Przystawik Andreas , Ribič Primož Rebernik , Sansone Giuseppe , Sigalotti Paolo , Spampinati Simone , Spezzani Carlo , Squibb Richard James , Stranges Stefano , Uhl Daniel , Stienkemeier Frank 
Published: February 2020

AbstractThe recent development of ultrafast extreme ultraviolet (XUV) coherent light sources bears great potential for a better understanding of the structure and dynamics of matter. Promising routes are advanced coherent control and nonlinear spectroscopy schemes in the XUV energy range, yielding unprecedented spatial and temporal resolution. However, their implementation has been hampered by the experimental challenge of generating XUV pulse sequences with precisely controlled timing and phase properties. In particular, direct control and manipulation of the phase of individual pulses within an XUV pulse sequence opens exciting possibilities for coherent control and multidimensional spectroscopy, but has not been accomplished. Here, we overcome these constraints in a highly time-stabilized and phase-modulated XUV-pump, XUV-probe experiment, which directly probes the evolution and dephasing of an inner subshell electronic coherence. This approach, avoiding any XUV optics for direct pulse manipulation, opens up extensive applications of advanced nonlinear optics and spectroscopy at XUV wavelengths.
Structural insights into NDH-1 mediated cyclic electron transfer
Authors: Zhang Chunli , Shuai Jin , Ran Zhaoxing , Zhao Jiaohong , Wu Zhenfang , Liao Rijing , Wu Jian , Ma Weimin , Lei Ming 
Published: February 2020

AbstractNDH-1 is a key component of the cyclic-electron-transfer around photosystem I (PSI CET) pathway, an important antioxidant mechanism for efficient photosynthesis. Here, we report a 3.2-Å-resolution cryo-EM structure of the ferredoxin (Fd)-NDH-1L complex from the cyanobacterium Thermosynechococcus elongatus. The structure reveals three β-carotene and fifteen lipid molecules in the membrane arm of NDH-1L. Regulatory oxygenic photosynthesis-specific (OPS) subunits NdhV, NdhS and NdhO are close to the Fd-binding site whilst NdhL is adjacent to the plastoquinone (PQ) cavity, and they play different roles in PSI CET under high-light stress. NdhV assists in the binding of Fd to NDH-1L and accelerates PSI CET in response to short-term high-light exposure. In contrast, prolonged high-light irradiation switches on the expression and assembly of the NDH-1MS complex, which likely contains no NdhO to further accelerate PSI CET and reduce ROS production. We propose that this hierarchical mechanism is necessary for the survival of cyanobacteria in an aerobic environment.
Exercise enhances skeletal muscle regeneration by promoting senescence in fibro-adipogenic progenitors
Authors: Saito Yuki , Chikenji Takako S. , Matsumura Takashi , Nakano Masako , Fujimiya Mineko 
Published: February 2020

AbstractIdiopathic inflammatory myopathies cause progressive muscle weakness and degeneration. Since high-dose glucocorticoids might not lead to full recovery of muscle function, physical exercise is also an important intervention, but some exercises exacerbate chronic inflammation and muscle fibrosis. It is unknown how physical exercise can have both beneficial and detrimental effects in chronic myopathy. Here we show that senescence of fibro-adipogenic progenitors (FAPs) in response to exercise-induced muscle damage is needed to establish a state of regenerative inflammation that induces muscle regeneration. In chronic inflammatory myopathy model mice, exercise does not promote FAP senescence or resistance against tumor necrosis factor–mediated apoptosis. Pro-senescent intervention combining exercise and pharmacological AMPK activation reverses FAP apoptosis resistance and improves muscle function and regeneration. Our results demonstrate that the absence of FAP senescence after exercise leads to muscle degeneration with FAP accumulation. FAP-targeted pro-senescent interventions with exercise and pharmacological AMPK activation may constitute a therapeutic strategy for chronic inflammatory myopathy.
Perovskite-molecule composite thin films for efficient and stable light-emitting diodes
Authors: Wang Heyong , Kosasih Felix Utama , Yu Hongling , Zheng Guanhaojie , Zhang Jiangbin , Pozina Galia , Liu Yang , Bao Chunxiong , Hu Zhangjun , Liu Xianjie , Kobera Libor , Abbrent Sabina , Brus Jiri , Jin Yizheng , Fahlman Mats , Friend Richard H. , Ducati Caterina , Liu Xiao-Ke , Gao Feng 
Published: February 2020

AbstractAlthough perovskite light-emitting diodes (PeLEDs) have recently experienced significant progress, there are only scattered reports of PeLEDs with both high efficiency and long operational stability, calling for additional strategies to address this challenge. Here, we develop perovskite-molecule composite thin films for efficient and stable PeLEDs. The perovskite-molecule composite thin films consist of in-situ formed high-quality perovskite nanocrystals embedded in the electron-transport molecular matrix, which controls nucleation process of perovskites, leading to PeLEDs with a peak external quantum efficiency of 17.3% and half-lifetime of approximately 100 h. In addition, we find that the device degradation mechanism at high driving voltages is different from that at low driving voltages. This work provides an effective strategy and deep understanding for achieving efficient and stable PeLEDs from both material and device perspectives.
Bayesian Spatiotemporal Modeling of Routinely Collected Data to Assess the Effect of Health Programs in Malaria Incidence During Pregnancy in Burkina Faso
Authors: Rouamba Toussaint , Samadoulougou Sekou , Tinto Halidou , Alegana Victor A. , Kirakoya-Samadoulougou Fati 
Published: February 2020

AbstractControl of malaria in pregnancy (MiP) remains a major challenge in Burkina Faso. Surveillance of the burden due to MiP based on routinely collected data at a fine-scale level, followed by an appropriate analysis and interpretation, may be crucial for evaluating and improving the effectiveness of existing control measures. We described the spatio-temporal dynamics of MiP at the community-level and assessed health program effects, mainly community-based health promotion, results-based financing, and intermittent-preventive-treatment with sulphadoxine-pyrimethamine (IPTp-SP). Community-aggregated monthly MiP cases were downloaded from Health Management Information System and combined with covariates from other sources. The MiP spatio-temporal pattern was decomposed into three components: overall spatial and temporal trends and space-time interaction. Bayesian hierarchical spatio-temporal Poisson models were used to fit the MiP incidence rate and assess health program effects. The overall annual incidence increased between 2015 and 2017. The findings reveal spatio-temporal heterogenicity throughout the year, which peaked during rainy season. From the model without covariates, 96 communities located mainly in the Cascades, South-West, Center-West, Center-East, and Eastern regions, exhibited significant relative-risk levels. The combined effect (significant reducing effect) of RBF, health promotion and IPTp-SP strategies was greatest in 17.7% (17/96) of high burden malaria communities. Despite intensification of control efforts, MiP remains high at the community-scale. The provided risk maps are useful tools for highlighting areas where interventions should be optimized, particularly in high-risk communities.
Concentration dependence of the sol-gel phase behavior of agarose-water system observed by the optical bubble pressure tensiometry
Authors: Ichinose Nobuyuki , Ura Hodaka 
Published: February 2020

AbstractWe have studied an expansion behavior of pressurized bubbles at the orifice of a capillary inserted in gelator-solvent (agarose-water) mixtures as a function of the gelator concentration in which the phase transition points are included. The pressure (P) -dependence of the radius of the curvature (R) of the bubbles monitored by laser beam has shown a discontinuous decrease in the exponent (m) of the experimental power law R = KΔP−m (K: constant) from 1 to 1/2 and a discontinuous increase in the average surface tension (γave) obtained from the work-area plots of the mixtures exceeding that of pure water (72.6 mN/m) at 0.02 < [agarose] < 0.03 wt%, which is attributed to the disappearance of the fluidity. The apparent surface tension (γapp = ΔP/2 R) of the system in the concentration range of 0.03–0.20 wt% has been analyzed by a modified Shuttleworth equation γapp = σ0 + τln(A/A0), where σ0 is an isotropic constant component and the second term is a surface area (A) -dependent elastic component, in which τ is the coefficient and A0 is the area of the orifice. The analysis has indicated that σ0 coincides with the γapp value of the mixture of 0.02 wt% and the second term at >0.02 wt% is the dominant component. From the appearance of the elastic component and concentration dependence of τ, the plateau of τ for the agarose-water mixtures at 0.03–0.10 wt% (Region II) has been explained to the phase separation giving two-phase mixtures of 0.02 wt% sol and 0.10 wt% gel and the upward inflection of τ at 0.10 wt% has been assigned to an increase in the elasticity of the gel with the increase of the agarose concentration in the range of >0.10 wt% (Region III). On considering the concentration dependence of the surface tension of agarose-water mixtures, the discontinuous and inflection points were assigned to the 1st- and 2nd-order phase transition concentrations of the agarose gel, respectively. Given the results with our tensiometry based on the optical bubble pressure method, distinct gelation points for other systems could be determined both mechanically and thermodynamically which will provide a diagnostic criterion of sol-gel transitions.
Surveillance-embedded genomic outbreak resolution of methicillin-susceptible Staphylococcus aureus in a neonatal intensive care unit
Authors: Cremers A. J. H. , Coolen J. P. M. , Bleeker-Rovers C. P. , van der Geest-Blankert A. D. J. , Haverkate D. , Hendriks H. , Henriet S. S. V. , Huynen M. A. , Kolwijck E. , Liem D. , Melchers W. J. G. , Rossen J. W. , Zoll J. , van Heijst A. , Hopman J. , Wertheim H. F. L. 
Published: February 2020

AbstractWe observed an increase in methicillin-susceptible Staphylococcus aureus (MSSA) infections at a Dutch neonatal intensive care unit. Weekly neonatal MSSA carriage surveillance and cross-sectional screenings of health care workers (HCWs) were available for outbreak tracing. Traditional clustering of MSSA isolates by spa typing and Multiple-Locus Variable number tandem repeat Analysis (MLVA) suggested that nosocomial transmission had contributed to the infections. We investigated whether whole-genome sequencing (WGS) of MSSA surveillance would provide additional evidence for transmission. MSSA isolates from neonatal infections, carriage surveillance, and HCWs were subjected to WGS and bioinformatic analysis for identification and localization of high-quality single nucleotide polymorphisms, and in-depth analysis of subsets of isolates. By measuring the genetic diversity in background surveillance, we defined transmission-level relatedness and identified isolates that had been unjustly assigned to clusters based on MLVA, while spa typing was concordant but of insufficient resolution. Detailing particular subsets of isolates provided evidence that HCWs were involved in multiple outbreaks, yet it alleviated concerns about one particular HCW. The improved resolution and accuracy of genomic outbreak analyses substantially altered the view on outbreaks, along with apposite measures. Therefore, inclusion of the circulating background population has the potential to overcome current issues in genomic outbreak inference.
Frailness and resilience of gene networks predicted by detection of co-occurring mutations via a stochastic perturbative approach
Authors: Bersanelli Matteo , Mosca Ettore , Milanesi Luciano , Bazzani Armando , Castellani Gastone 
Published: February 2020

AbstractIn recent years complex networks have been identified as powerful mathematical frameworks for the adequate modeling of many applied problems in disparate research fields. Assuming a Master Equation (ME) modeling the exchange of information within the network, we set up a perturbative approach in order to investigate how node alterations impact on the network information flow. The main assumption of the perturbed ME (pME) model is that the simultaneous presence of multiple node alterations causes more or less intense network frailties depending on the specific features of the perturbation. In this perspective the collective behavior of a set of molecular alterations on a gene network is a particularly adapt scenario for a first application of the proposed method, since most diseases are neither related to a single mutation nor to an established set of molecular alterations. Therefore, after characterizing the method numerically, we applied as a proof of principle the pME approach to breast cancer (BC) somatic mutation data downloaded from Cancer Genome Atlas (TCGA) database. For each patient we measured the network frailness of over 90 significant subnetworks of the protein-protein interaction network, where each perturbation was defined by patient-specific somatic mutations. Interestingly the frailness measures depend on the position of the alterations on the gene network more than on their amount, unlike most traditional enrichment scores. In particular low-degree mutations play an important role in causing high frailness measures. The potential applicability of the proposed method is wide and suggests future development in the control theory context.