bluuebunny/crossref_metadata_2025_split huggingface dataset:
RAF proteins exert both specific and compensatory functions during tumour progression of NRAS-driven melanoma
Authors: Dorard Coralie , Estrada Charlène , Barbotin Céline , Larcher Magalie , Garancher Alexandra , Leloup Jessy , Beermann Friedrich , Baccarini Manuela , Pouponnot Celio , Larue Lionel , Eychène Alain , Druillennec Sabine 
Published: May 2017

AbstractNRAS and its effector BRAF are frequently mutated in melanoma. Paradoxically, CRAF but not BRAF was shown to be critical for various RAS-driven cancers, raising the question of the role of RAF proteins in NRAS-induced melanoma. Here, using conditional ablation of Raf genes in NRAS-induced mouse melanoma models, we investigate their contribution in tumour progression, from the onset of benign tumours to malignant tumour maintenance. We show that BRAF expression is required for ERK activation and nevi development, demonstrating a critical role in the early stages of NRAS-driven melanoma. After melanoma formation, single Braf or Craf ablation is not sufficient to block tumour growth, showing redundant functions for RAF kinases. Finally, proliferation of resistant cells emerging in the absence of BRAF and CRAF remains dependent on ARAF-mediated ERK activation. These results reveal specific and compensatory functions for BRAF and CRAF and highlight an addiction to RAF signalling in NRAS-driven melanoma.
Quantum vertex model for reversible classical computing
Authors: Chamon C. , Mucciolo E. R. , Ruckenstein A. E. , Yang Z.-C. 
Published: May 2017

AbstractMappings of classical computation onto statistical mechanics models have led to remarkable successes in addressing some complex computational problems. However, such mappings display thermodynamic phase transitions that may prevent reaching solution even for easy problems known to be solvable in polynomial time. Here we map universal reversible classical computations onto a planar vertex model that exhibits no bulk classical thermodynamic phase transition, independent of the computational circuit. Within our approach the solution of the computation is encoded in the ground state of the vertex model and its complexity is reflected in the dynamics of the relaxation of the system to its ground state. We use thermal annealing with and without ‘learning’ to explore typical computational problems. We also construct a mapping of the vertex model into the Chimera architecture of the D-Wave machine, initiating an approach to reversible classical computation based on state-of-the-art implementations of quantum annealing.
Locus-specific histone deacetylation using a synthetic CRISPR-Cas9-based HDAC
Authors: Kwon Deborah Y. , Zhao Ying-Tao , Lamonica Janine M. , Zhou Zhaolan 
Published: May 2017

AbstractEfforts to manipulate locus-specific histone acetylation to assess their causal role in gene expression and cellular and behavioural phenotypes have been impeded by a lack of experimental tools. The Cas9 nuclease has been adapted to target epigenomic modifications, but a detailed description of the parameters of such synthetic epigenome remodellers is still lacking. Here we describe a Cas9-based histone deacetylase (HDAC) and the design principles required to achieve locus-specific histone deacetylation. We assess its range of activity and specificity, and analyse target gene expression in two different cell types to investigate cellular context-dependent effects. Our findings demonstrate that the chromatin environment is an important element to consider when utilizing this synthetic HDAC.
Reciprocal regulation of the Il9 locus by counteracting activities of transcription factors IRF1 and IRF4
Authors: Campos Carrascosa Lucia , Klein Matthias , Kitagawa Yohko , Lückel Christina , Marini Federico , König Anika , Guralnik Anna , Raifer Hartmann , Hagner-Benes Stefanie , Rädler Diana , Böck Andreas , Kang Cholho , Lohoff Michael , Garn Holger , Schaub Bianca , Berberich-Siebelt Friederike , Sakaguchi Shimon , Bopp Tobias , Huber Magdalena 
Published: May 2017

AbstractThe T helper 9 (Th9) cell transcriptional network is formed by an equilibrium of signals induced by cytokines and antigen presentation. Here we show that, within this network, two interferon regulatory factors (IRF), IRF1 and IRF4, display opposing effects on Th9 differentiation. IRF4 dose-dependently promotes, whereas IRF1 inhibits, IL-9 production. Likewise, IRF1 inhibits IL-9 production by human Th9 cells. IRF1 counteracts IRF4-drivenIl9promoter activity, and IRF1 and IRF4 have opposing function on activating histone modifications, thus modulating RNA polymerase II recruitment. IRF1 occupancy correlates with decreased IRF4 abundance, suggesting an IRF1-IRF4-binding competition at theIl9locus. Furthermore, IRF1 shapes Th9 cells with an interferon/Th1 gene signature. Consistently, IRF1 restricts the IL-9-dependent pathogenicity of Th9 cells in a mouse model of allergic asthma. Thus our study reveals that the molecular ratio between IRF4 and IRF1 balances Th9 fate, thus providing new possibilities for manipulation of Th9 differentiation.
Potent antitumour activity of interleukin-2-Fc fusion proteins requires Fc-mediated depletion of regulatory T-cells
Authors: Vazquez-Lombardi Rodrigo , Loetsch Claudia , Zinkl Daniela , Jackson Jennifer , Schofield Peter , Deenick Elissa K. , King Cecile , Phan Tri Giang , Webster Kylie E. , Sprent Jonathan , Christ Daniel 
Published: May 2017

AbstractInterleukin-2 (IL-2) is an established therapeutic agent used for cancer immunotherapy. Since treatment efficacy is mediated by CD8+and NK cell activity at the tumour site, considerable efforts have focused on generating variants that expand these subsets systemically, as exemplified by IL-2/antibody complexes and ‘superkines’. Here we describe a novel determinant of antitumour activity using fusion proteins consisting of IL-2 and the antibody fragment crystallizable (Fc) region. Generation of long-lived IL-2-Fc variants in which CD25 binding is abolished through mutation effectively prevents unwanted activation of CD25+regulatory T-cells (Tregs) and results in strong expansion of CD25−cytotoxic subsets. Surprisingly, however, such variants are less effective than wild-type IL-2-Fc in mediating tumour rejection. Instead, we report that efficacy is crucially dependent on depletion of Tregs through Fc-mediated immune effector functions. Our results underpin an unexpected mechanism of action and provide important guidance for the development of next generation IL-2 therapeutics.
A TRIM insertion in the promoter of Ms2 causes male sterility in wheat
Authors: Xia Chuan , Zhang Lichao , Zou Cheng , Gu Yongqiang , Duan Jialei , Zhao Guangyao , Wu Jiajie , Liu Yue , Fang Xiaohua , Gao Lifeng , Jiao Yuannian , Sun Jiaqiang , Pan Yinghong , Liu Xu , Jia Jizeng , Kong Xiuying 
Published: May 2017

AbstractThe male-sterile ms2 mutant has been known for 40 years and has become extremely important in the commercial production of wheat. However, the gene responsible for this phenotype has remained unknown. Here we report the map-based cloning of the Ms2 gene. The Ms2 locus is remarkable in several ways that have implications in basic biology. Beyond having no functional annotation, barely detectable transcription in fertile wild-type wheat plants, and accumulated destructive mutations in Ms2 orthologs, the Ms2 allele in the ms2 mutant has acquired a terminal-repeat retrotransposon in miniature (TRIM) element in its promoter. This TRIM element is responsible for the anther-specific Ms2 activation that confers male sterility. The identification of Ms2 not only unravels the genetic basis of a historically important breeding trait, but also shows an example of how a TRIM element insertion near a gene can contribute to genetic novelty and phenotypic plasticity.
Expression and Activity of the BioH Esterase of Biotin Synthesis is Independent of Genome Context
Authors: Cao Xinyun , Zhu Lei , Hu Zhe , Cronan John E. 
Published: May 2017

AbstractBioH is an α/β-hydrolase required for synthesis of the pimelate moiety of biotin in diverse bacteria. The bioH gene is found in different genomic contexts. In some cases (e.g., Escherichia coli) the gene is not located within a biotin synthetic operon and its transcription is not coregulated with the other biotin synthesis genes. In other genomes such as Pseudomonas aeruginosa the bioH gene is within a biotin synthesis operon and its transcription is coregulated with the other biotin operon genes. The esterases of pimelate moiety synthesis show remarkable genomic plasticity in that in some biotin operons bioH is replaced by other α/ß hydrolases of diverse sequence. The “wild card” nature of these enzymes led us to compare the paradigm “freestanding” E. coli BioH with the operon-encoded P. aeruginosa BioH. We hypothesized that the operon-encoded BioH might differ in its expression level and/or activity from the freestanding BioH gene. We report this is not the case. The two BioH proteins show remarkably similar hydrolase activities and substrate specificity. Moreover, Pseudomonas aeruginosa BioH is more highly expressed than E. coli BioH. Despite the enzymatic similarities of the two BioH proteins, bioinformatics analysis places the freestanding and operon-encoded BioH proteins into distinct clades.
Mapping anomalous dispersion of air with ultrashort mid-infrared pulses
Authors: Mitrofanov A. V. , Voronin A. A. , Sidorov-Biryukov D. A. , Rozhko M. V. , Stepanov E. A. , Fedotov A. B. , Shumakova V. , Ališauskas S. , Pugžlys A. , Baltuška A. , Zheltikov A. M. 
Published: May 2017

AbstractWe present experimental studies of long-distance transmission of ultrashort mid-infrared laser pulses through atmospheric air, probing air dispersion in the 3.6–4.2-μm wavelength range. Atmospheric air is still highly transparent to electromagnetic radiation in this spectral region, making it interesting for long-distance signal transmission. However, unlike most of the high-transmission regions in gas media, the group-velocity dispersion, as we show in this work, is anomalous at these wavelengths due to the nearby asymmetric-stretch rovibrational band of atmospheric carbon dioxide. The spectrograms of ultrashort mid-infrared laser pulses transmitted over a distance of 60 m in our experiments provide a map of air dispersion in this wavelength range, revealing clear signatures of anomalous dispersion, with anomalous group delays as long as 1.8 ps detected across the bandwidth covered by 80-fs laser pulses.
Emotional Contexts Exert a Distracting Effect on Attention and Inhibitory Control in Female and Male Adolescents
Authors: Ramos-Loyo Julieta , Llamas-Alonso Luis A. , González-Garrido Andrés A. , Hernández-Villalobos Juan 
Published: May 2017

AbstractAdolescents exhibit difficulties in behavioral regulation that become more evident when emotional contexts are involved, since these may hinder the development of socially-adaptive behaviors. The objectives of the present study were: to examine the influence of emotional contexts on adolescents’ ability to inhibit a prepotent response, evaluated by ERPs, and to determine whether sex differences in response inhibition are observed in adolescents in those contexts. Participants performed a prepotent response inhibition task (Go-NoGo) under 3 background context conditions: neutral, pleasant, and unpleasant. While no differences in accuracy were observed, the presence of emotional contexts did prolong reaction times compared to the neutral context. Also, the unpleasant context caused an enhancement of N2 amplitudes compared to the neutral and pleasant contexts. Also, N2 and P3 latencies were longer in emotional contexts than in the neutral condition during both correct responses and correct inhibitions. No sex differences were found in amplitude, but females showed longer N2 and P3 latencies than males. These results confirm the idea that, in adolescents, unpleasant pictures receive preferential attention over neutral images and so generate greater difficulty in response inhibition. Finally, results demonstrate that sex differences in inhibition control in adolescence were observed only in relation to time-processing.
Scaling of average receiving time on weighted polymer networks with some topological properties
Authors: Ye Dandan , Liu Song , Li Jia , Zhang Fei , Han Changling , Chen Wei , Zhang Yingze 
Published: May 2017

AbstractIn this paper, a family of the weighted polymer networks is introduced depending on the number of copies f and a weight factor r. The topological properties of weighted polymer networks can be completely analytically characterized in terms of the involved parameters and/or of the fractal dimension. Moreover, assuming that the walker, at each step, starting from its current node, moves to any of its neighbors with probability proportional to the weight of edge linking them, namely weight-dependent walk. Then, we calculate the average receiving time (ART) with weighted-dependent walks, which is the sum of mean first-passage times (MFPTs) for all nodes absorpt at the trap located at the central node as a recursive relation. The obtained remarkable results display that when $$\frac{1}{f+1} < r < 1$$

1

f
+
1

<
r
<
1
, the ART grows sublinearly with the network size; when $$r=\frac{1}{f+1}$$
r
=

1

f
+
1

, ART grows with increasing size N
g
as $${\mathrm{ln}}^{2}{N}_{g}$$

ln

2

N

g

; when $$0 < r < \frac{1}{f+1}$$
0
<
r
<

1

f
+
1

, ART grows with increasing size N
g
as ln N
g
. In the treelike polymer networks, ART grows with linearly with the network size N
g
when r = 1. Thus, the weighted polymer networks are more efficient than treelike polymer networks in receiving information.
Enhanced sulfidation xanthate flotation of malachite using ammonium ions as activator
Authors: Wu Dandan , Ma Wenhui , Mao Yingbo , Deng Jiushuai , Wen Shuming 
Published: May 2017

AbstractIn this study, ammonium ion was used to enhance the sulfidation flotation of malachite. The effect of ammonium ion on the sulfidation flotation of malachite was investigated using microflotation test, inductively coupled plasma (ICP) analysis, zeta potential measurements, and scanning electron microscope analysis (SEM). The results of microflotation test show that the addition of sodium sulfide and ammonium sulfate resulted in better sulfidation than the addition of sodium sulfide alone. The results of ICP analysis indicate that the dissolution of enhanced sulfurized malachite surface is significantly decreased. Zeta potential measurements indicate that a smaller isoelectric point value and a large number of copper-sulfide films formed on the malachite surface by enhancing sulfidation resulted in a large amount of sodium butyl xanthate absorbed onto the enhanced sulfurized malachite surface. EDS semi-quantitative analysis and XPS analysis show that malachite was easily sulfurized by sodium sulfide with ammonium ion. These results show that the addition of ammonium ion plays a significant role in the sulfidation of malachite and results in improved flotation performance.
Integrated trophic position decreases in more diverse communities of stream food webs
Authors: Ishikawa Naoto F. , Chikaraishi Yoshito , Ohkouchi Naohiko , Murakami Aya R. , Tayasu Ichiro , Togashi Hiroyuki , Okano Jun-ichi , Sakai Yoichiro , Iwata Tomoya , Kondoh Michio , Okuda Noboru 
Published: May 2017

AbstractThe relationship between biodiversity and ecosystem functioning is an important theme in environmental sciences. We propose a new index for configuration of the biomass pyramid in an ecosystem, named integrated trophic position (iTP). The iTP is defined as a sum of trophic positions (i.e. the average number of steps involved in biomass transfer) of all the animals in a food web integrated by their individual biomass. The observed iTP for stream macroinvertebrates ranged from 2.39 to 2.79 and was negatively correlated with the species density and the Shannon–Wiener diversity index of the local community. The results indicate a lower efficiency of biomass transfer in more diverse communities, which may be explained by the variance in edibility hypothesis and/or the trophic omnivory hypothesis. We found a negative effect of biodiversity on ecosystem functioning.
Kup-mediated Cs+ uptake and Kdp-driven K+ uptake coordinate to promote cell growth during excess Cs+ conditions in Escherichia coli
Authors: Tanudjaja Ellen , Hoshi Naomi , Su Yi-Hsin , Hamamoto Shin , Uozumi Nobuyuki 
Published: May 2017

AbstractThe physiological effects of caesium (Cs) on living cells are poorly understood. Here, we examined the physiological role of Cs+ on the activity of the potassium transporters in E. coli. In the absence of potassium (K+), Kup-mediated Cs+ uptake partially supported cell growth, however, at a much lower rate than with sufficient K+. In K+-limited medium (0.1 mM), the presence of Cs+ (up to 25 mM) in the medium enhanced growth as much as control medium containing 1 mM K+. This effect depended on the maintenance of basal levels of intracellular K+ by other K+ uptake transporters. Higher amounts of K+ (1 mM) in the medium eliminated the positive effect of Cs+ on growth, and revealed the inhibitory effect of high Cs+ on the growth of wild-type E. coli. Cells lacking Kdp, TrkG and TrkH but expressing Kup grew less well when Cs+ was increased in the medium. A kdp mutant contained an increased ratio of Cs+/K+ in the presence of high Cs+ in the medium and consequently was strongly inhibited in growth. Taken together, under excess Cs+ conditions Kup-mediated Cs+ influx sustains cell growth, which is supported by intracellular K+ supplied by Kdp.
Diagnosing congenital malaria in a high-transmission setting: clinical relevance and usefulness of P. falciparum HRP2-based testing
Authors: Natama Hamtandi Magloire , Ouedraogo Delwendé Florence , Sorgho Hermann , Rovira-Vallbona Eduard , Serra-Casas Elisa , Somé M. Athanase , Coulibaly-Traoré Maminata , Mens Petra F. , Kestens Luc , Tinto Halidou , Rosanas-Urgell Anna 
Published: May 2017

AbstractCongenital malaria diagnosis is challenging due to frequently observed low parasite density infections, while their clinical relevance during early infancy is not well characterized. In Nanoro health district (Burkina Faso), we determined the prevalence of congenital malaria by real-time quantitative PCR and we assessed the performance of rapid diagnosis test (RDT) and light microscopy (LM) to detect Plasmodium falciparum infections in cord-blood samples. In addition, we examined the usefulness of P. falciparum Histidine Rich Protein2 (PfHRP2) as surrogate biomarker of infection and explored association between congenital malaria and clinical outcomes. A prevalence of congenital malaria by qPCR of 4% (16/400) was found, which increased to 10% among newborns from mothers infected at delivery. RDT and LM showed poor performances indicating limited utility for congenital malaria screening in cord blood. Because PfHRP2 detection in cord blood could be affected by transplacental passage of parasite antigens, PfHRP2 might not be used as a surrogate biomarker of congenital malaria infections. There was no evidence of a significant clinical impact of congenital malaria on infant’s health from birth to 59 days of life. Case control studies including long-term follow up may provide additional understanding on the relevance of neonatal malaria infections.
Microstructures, mechanical behavior and strengthening mechanism of TiSiCN nanocomposite films
Authors: Li Wei , Liu Ping , Xue Zenghui , Ma Fengcang , Zhang Ke , Chen Xiaohong , Feng Rui , Liaw Peter K. 
Published: May 2017

AbstractCurrently, the arguments have existed in the strengthening mechanism and microstructural model of the nanocomposite film due to lack of the convincible experimental evidences. In this investigation, the quarternary TiSiCN nanocomposite films with the different C and Si contents are synthesized by the reactive-magnetron-sputtering technique. The TiSiCN film is characterized as the nanocomposite structure with the TiN nanocrystallites surrounded by the (Si3N4 + C + CNx) interface phase. When the C/Si content ratio is 2:2, the TiSiCN nanocomposite film is remarkably strengthened with the maximal hardness and elastic modulus of 46.1 GPa and 425 GPa, respectively. Meanwhile, the (Si3N4 + C + CNx) interfaces exhibit as a crystallized form, which can coordinate the growth misorientations and maintain the coherently epitaxial growth between the TiN nanocrystallites and interfaces. Through the high-resolution transmission electron microscopy (HRTEM) observations, this investigation firstly provides the direct experimental evidence for the crystallized feature of the interfaces when the TiSiCN nanocomposite film is strengthened, suggesting that the strengthening effect of the TiSiCN nanocomposite film can be attributed to the coherent-interface strengthening mechanism, which is expressed as the “nc-TiN/c-Si3N4/c-C/c-CNx” model.
MUG-Mel2, a novel highly pigmented and well characterized NRAS mutated human melanoma cell line
Authors: Rinner Beate , Gandolfi Greta , Meditz Katharina , Frisch Marie-Therese , Wagner Karin , Ciarrocchi Alessia , Torricelli Federica , Koivuniemi Raili , Niklander Johanna , Liegl-Atzwanger Bernadette , Lohberger Birgit , Heitzer Ellen , Ghaffari-Tabrizi-Wizsy Nassim , Zweytick Dagmar , Zalaudek Iris 
Published: May 2017

AbstractNRAS mutation in melanoma has been associated with aggressive tumor biology and poor prognosis. Although targeted therapy has been tested for NRAS mutated melanoma, response rates still appear much weaker, than in BRAF mutated melanoma. While plenty of cell lines exist, however, only few melanogenic cell lines retain their in vivo characteristics. In this work we present an intensively pigmented and well-characterized cell line derived from a highly aggressive NRAS mutated cutaneous melanoma, named MUG-Mel2. We present the clinical course, unique morphology, angiogenic properties, growth characteristics using in vivo experiments and 3D cell culture, and results of the exome gene sequencing of an intensively pigmented melanogenic cell line MUG-Mel2, derived from a cutaneous metastasis of an aggressive NRAS p. Q61R mutated melanoma. Amongst several genetic alterations, mutations in GRIN2A, CREBP, PIK3C2G, ATM, and ATR were present. These mutations, known to reinforce DNA repair problems in melanoma, might serve as potential treatment targets. The aggressive and fast growing behavior in animal models and the obtained phenotype in 3D culture reveal a perfect model for research in the field of NRAS mutated melanoma.
3D micro-structured arrays of ZnΟ nanorods
Authors: Giakoumaki Argyro N. , Kenanakis George , Klini Argyro , Androulidaki Maria , Viskadourakis Zacharias , Farsari Maria , Selimis Alexandros 
Published: May 2017

AbstractThe fabrication of nanostructures with controlled assembly and architecture is very important for the development of novel nanomaterial-based devices. We demonstrate that laser techniques coupled with low-temperature hydrothermal growth enable complex three-dimensional ZnO nanorod patterning on various types of substrates and geometries. This methodology is based on a procedure involving the 3D scaffold fabrication using Multi-Photon Lithography of a photosensitive material, followed by Zn seeded Aqueous Chemical Growth of ZnO nanorods. 3D, uniformly aligned ZnO nanorods are produced. The increase in active surface area, up to 4.4 times in the cases presented here, provides a dramatic increase in photocatalytic performance, while other applications are also proposed.