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See detailAutomated microfluidic cell culture of stem cell derived dopaminergic neurons
Kane, Khalid; Lucumi Moreno, Edinson; Hachi, Siham et al

in Scientific Reports (2019)

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See detailTunable magnetoplasmonics in lattices of Ni/SiO2/Au dimers
Pourjamal, Sara; Kataja, Mikko; Maccaferri, Nicolò UL et al

in Scientific Reports (2019), 9

We present a systematic study on the optical and magneto-optical properties of Ni/SiO2/Au dimer lattices. By consideringthe excitation of orthogonal dipoles in the Ni and Au nanodisks, we analytically ... [more ▼]

We present a systematic study on the optical and magneto-optical properties of Ni/SiO2/Au dimer lattices. By consideringthe excitation of orthogonal dipoles in the Ni and Au nanodisks, we analytically demonstrate that the magnetoplasmonicresponse of dimer lattices is governed by a complex interplay of near- and far-field interactions. Near-field coupling betweendipoles in Ni and low-loss Au enhances the polarizabilty of single dimers compared to that of isolated Ni nanodisks. Far-fielddiffractive coupling in periodic lattices of these two particle types enlarges the difference in effective polarizability further.This effect is explained by an inverse relationship between the damping of collective surface lattice resonances and theimaginary polarizability of individual scatterers. Optical reflectance measurements, magneto-optical Kerr effect spectra, andfinite-difference time-domain simulations confirm the analytical results. Hybrid dimer arrays supporting intense plasmonexcitations are a promising candidate for active magnetoplasmonic devices. [less ▲]

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See detailAutomated high-throughput highcontent autophagy and mitophagy analysis platform
Arias-Fuenzalida, Jonathan; Jarazo, Javier UL; Walter, Jonas et al

in Scientific Reports (2019)

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See detailThe intertwined metabolism during symbiotic nitrogen fixation elucidated by metabolic modelling
Pfau, Thomas UL; Christian, Nils UL; Masakapalli, Shyam K. et al

in Scientific Reports (2018), 8

Genome-scale metabolic network models can be used for various analyses including the prediction of metabolic responses to changes in the environment. Legumes are well known for their rhizobial symbiosis ... [more ▼]

Genome-scale metabolic network models can be used for various analyses including the prediction of metabolic responses to changes in the environment. Legumes are well known for their rhizobial symbiosis that introduces nitrogen into the global nutrient cycle. Here, we describe a fully compartmentalised, mass and charge-balanced, genome-scale model of the clover Medicago truncatula, which has been adopted as a model organism for legumes. We employed flux balance analysis to demonstrate that the network is capable of producing biomass components in experimentally observed proportions, during day and night. By connecting the plant model to a model of its rhizobial symbiont, Sinorhizobium meliloti, we were able to investigate the effects of the symbiosis on metabolic fluxes and plant growth and could demonstrate how oxygen availability influences metabolic exchanges between plant and symbiont, thus elucidating potential benefits of inter organism amino acid cycling. We thus provide a modelling framework, in which the interlinked metabolism of plants and nodules can be studied from a theoretical perspective. [less ▲]

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See detailLive Intracellular Biorthogonal Imaging by Surface Enhanced Raman Spectroscopy using Alkyne-Silver Nanoparticles Clusters
Ardini, Matteo; Huang, Jian-An; Sanchez, Carlos S. et al

in Scientific Reports (2018), 8

Live intracellular imaging is a valuable tool in modern diagnostics and pharmacology. Surface Enhanced Raman Spectroscopy (SERS) stands out as a non-destructive and multiplexed technique, but ... [more ▼]

Live intracellular imaging is a valuable tool in modern diagnostics and pharmacology. Surface Enhanced Raman Spectroscopy (SERS) stands out as a non-destructive and multiplexed technique, but intracellular SERS imaging still suffers from interfering background from endogenous components. Here we show the assembly of small colloidal SERS probes with Raman signal in the cell-silent window of 1800–2900 cm−1 for biorthogonal intracellular SERS imaging of dopamine that was undistinguishable from the endogenous cell background. By linking colloidal silver nanoparticles with alkyne-dopamine adducts, clusters are formed by 2–6 nanoparticles spaced by tight interparticle gaps that exhibited high electric field enhancement and strong SERS signals of alkyne and dopamines. Due to the cell-silent signals of the alkyne, intracellular in-vitro Raman imaging shows that the dopamines on the internalized clusters remain distinguishable across the cytoplasm with good spatial resolution. Our method can be a general-purpose method for real-time imaging of biomolecules, such as proteins, peptides, DNA and drugs. [less ▲]

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See detailExpressed protein profile of a Tectomicrobium and other microbial symbionts in the marine sponge Aplysina aerophoba as evidenced by metaproteomics.
Chaib De Mares, Maryam; Jimenez, Diego Javier; Palladino, Giorgia et al

in Scientific reports (2018), 8(1), 11795

Aplysina aerophoba is an emerging model marine sponge, with a well-characterized microbial community in terms of diversity and structure. However, little is known about the expressed functional ... [more ▼]

Aplysina aerophoba is an emerging model marine sponge, with a well-characterized microbial community in terms of diversity and structure. However, little is known about the expressed functional capabilities of its associated microbes. Here, we present the first metaproteomics-based study of the microbiome of A. aerophoba. We found that transport and degradation of halogenated and chloroaromatic compounds are common active processes in the sponge microbiomes. Our data further reveal that the highest number of proteins were affiliated to a sponge-associated Tectomicrobium, presumably from the family Entotheonellaceae, as well as to the well-known symbiont "Candidatus Synechococcus spongiarium", suggesting a high metabolic activity of these two microorganisms in situ. Evidence for nitric oxide (NO) conversion to nitrous oxide was consistently observed for Tectomicrobia across replicates, by production of the NorQ protein. Moreover, we found a potential energy-yielding pathway through CO oxidation by putative Chloroflexi bacteria. Finally, we observed expression of enzymes that may be involved in the transformation of chitin, glycoproteins, glycolipids and glucans into smaller molecules, consistent with glycosyl hydrolases predicted from analyses of the genomes of Poribacteria sponge symbionts. Thus, this study provides crucial links between expressed proteins and specific members of the A. aerophoba microbiome. [less ▲]

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See detailOpposite feedback from mTORC1 to H-ras and K-ras4B downstream of SREBP1
Posada, IMD; Lectez, B; Siddiqui, FA et al

in Scientific Reports (2017)

As a major growth factor transducer, Ras is an upstream activator of mTORC1, which further integrates nutrient and energy inputs. To ensure a contextual coupling of cell division via Ras/MAPK-signalling ... [more ▼]

As a major growth factor transducer, Ras is an upstream activator of mTORC1, which further integrates nutrient and energy inputs. To ensure a contextual coupling of cell division via Ras/MAPK-signalling and growth via mTORC1-signalling, feedback loops from one pathway back to the other are required. Here we describe a novel feedback from mTORC1, which oppositely affects oncogenic H-ras- and K-ras-signalling output, and as a consequence stemness properties of tumourigenic cells. Amino acid stimulation of mTORC1 increases the processed form of SREBP1, a major lipidome regulator. We show that modulation of the SREBP1 levels downstream of S6K1 has opposite effects on oncogenic H-ras and K-ras nanoscale membrane organisation, ensuing signalling output and promotion of mammospheres expressing these oncogenes. Our data suggest that modulation of phosphatidic acid, a major target of SREBP1 controlled lipid metabolism, is sufficient to affect H-ras and K-ras oppositely in the membrane. Thus mTORC1 activation increases H-ras-, but decreases K-ras-signalling output in cells transformed with the respective oncogene. Given the different impact of these two Ras isoforms on stemness, our results could have implications for stem cell biology and inhibition of cancer stem cells. [less ▲]

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See detailThe buckling instability of aggregating red blood cells
Flomann, Daniel; Othmane, Aouane; Kaestner, Lars et al

in Scientific Reports (2017)

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See detailChiral Nematic Liquid Crystal Microlenses
Popov, Piotr; Honaker, Lawrence William UL; Mirheydari, Mona et al

in Scientific Reports (2017)

Nematic liquid crystals (NLCs) of achiral molecules and racemic mixtures of chiral ones form flat films and show uniform textures between circular polarizers when suspended in sub-millimeter size grids ... [more ▼]

Nematic liquid crystals (NLCs) of achiral molecules and racemic mixtures of chiral ones form flat films and show uniform textures between circular polarizers when suspended in sub-millimeter size grids and immersed in water. On addition of chiral dopants to the liquid crystal, the films exhibit optical textures with concentric ring patterns and radial variation of the birefringence color. Both are related to a biconvex shape of the chiral liquid crystal film; the rings are due to interference. The curvature radii of the biconvex lens array are in the range of a few millimeters. This curvature leads to a radial variation of the optical axis along the plane of the film. Such a Pancharatnam-type phase lens dominates the imaging and explains the measured focal length of about one millimeter. To our knowledge, these are the first spontaneously formed Pancharatnam devices. The unwinding of the helical structure at the grid walls drives the lens shape. The relation between the lens curvature and material properties such as helical pitch, the twist elastic constant, and the interfacial tensions, is derived. This simple, novel method for spontaneously forming microlens arrays can also be used for various sensors. [less ▲]

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See detailDeliberate and Accidental Gas-Phase Alkali Doping of Chalcogenide Semiconductors: Cu(In,Ga)Se2
Colombara, Diego UL; Berner, Ulrich; Ciccioli, Andrea et al

in Scientific Reports (2017), 7

Alkali metal doping is essential to achieve highly efficient energy conversion in Cu(In,Ga)Se2 (CIGSe) solar cells. Doping is normally achieved through solid state reactions, but recent observations of ... [more ▼]

Alkali metal doping is essential to achieve highly efficient energy conversion in Cu(In,Ga)Se2 (CIGSe) solar cells. Doping is normally achieved through solid state reactions, but recent observations of gas phase alkali transport in the kesterite sulfide (Cu2ZnSnS4) system (re)open the way to a novel gas-phase doping strategy. However, the current understanding of gas-phase alkali transport is very limited. This work (i) shows that CIGSe device efficiency can be improved from 2% to 8% by gas-phase sodium incorporation alone, (ii) identifies the most likely routes for gas-phase alkali transport based on mass spectrometric studies, (iii) provides thermochemical computations to rationalize the observations and (iv) critically discusses the subject literature with the aim to better understand the chemical basis of the phenomenon. These results suggest that accidental alkali metal doping occurs all the time, that a controlled vapor pressure of alkali metal could be applied during growth to dope the semiconductor, and that it may have to be accounted for during the currently used solid state doping routes. It is concluded that alkali gas-phase transport occurs through a plurality of routes and cannot be attributed to one single source. [less ▲]

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See detailSmall-angle neutron scattering modeling of spin disorder in nanoparticles
Vivas, Laura G.; Yanes, Rocio; Michels, Andreas UL

in Scientific Reports (2017), 7

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See detailFaithful SGCE imprinting in iPSC-derived cortical neurons: an endogenous cellular model of myoclonus-dystonia
Grütz, Karen; Weisbach, Anne; Lohmann, Katja et al

in Scientific Reports (2017)

In neuropathology research, induced pluripotent stem cell (iPSC)-derived neurons are considered a tool closely resembling the patient brain. Albeit in respect to epigenetics, this concept has been ... [more ▼]

In neuropathology research, induced pluripotent stem cell (iPSC)-derived neurons are considered a tool closely resembling the patient brain. Albeit in respect to epigenetics, this concept has been challenged. We generated iPSC-derived cortical neurons from myoclonus-dystonia patients with mutations (W100G and R102X) in the maternally imprinted ε-sarcoglycan (SGCE) gene and analysed properties such as imprinting, mRNA and protein expression. Comparison of the promoter during reprogramming and differentiation showed tissue-independent differential methylation. DNA sequencing with methylation-specific primers and cDNA analysis in patient neurons indicated selective expression of the mutated paternal SGCE allele. While fibroblasts only expressed the ubiquitous mRNA isoform, brain-specific SGCE mRNA and ε-sarcoglycan protein were detected in iPSC-derived control neurons. However, neuronal protein levels were reduced in both mutants. Our phenotypic characterization highlights the suitability of iPSC-derived cortical neurons with SGCE mutations for myoclonus-dystonia research and, in more general terms, prompts the use of iPSC-derived cellular models to study epigenetic mechanisms impacting on health and disease. [less ▲]

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See detailReliable and efficient solution of genome-scale models of Metabolism and macromolecular Expression
Ma, Ding; Yang, Laurence; Fleming, Ronan MT UL et al

in Scientific Reports (2017)

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See detailThe GBAP1 pseudogene acts as a ceRNA for the glucocerebrosidase gene GBA by sponging miR-22-3p.
Straniero, Letizia; Rimoldi, Valeria; Samarani, Maura et al

in Scientific reports (2017), 7(1), 12702

Mutations in the GBA gene, encoding lysosomal glucocerebrosidase, represent the major predisposing factor for Parkinson's disease (PD), and modulation of the glucocerebrosidase activity is an emerging PD ... [more ▼]

Mutations in the GBA gene, encoding lysosomal glucocerebrosidase, represent the major predisposing factor for Parkinson's disease (PD), and modulation of the glucocerebrosidase activity is an emerging PD therapy. However, little is known about mechanisms regulating GBA expression. We explored the existence of a regulatory network involving GBA, its expressed pseudogene GBAP1, and microRNAs. The high level of sequence identity between GBA and GBAP1 makes the pseudogene a promising competing-endogenous RNA (ceRNA), functioning as a microRNA sponge. After selecting microRNAs potentially targeting both transcripts, we demonstrated that miR-22-3p binds to and down-regulates GBA and GBAP1, and decreases their endogenous mRNA levels up to 70%. Moreover, over-expression of GBAP1 3'-untranslated region was able to sequester miR-22-3p, thus increasing GBA mRNA and glucocerebrosidase levels. The characterization of GBAP1 splicing identified multiple out-of-frame isoforms down-regulated by the nonsense-mediated mRNA decay, suggesting that GBAP1 levels and, accordingly, its ceRNA effect, are significantly modulated by this degradation process. Using skin-derived induced pluripotent stem cells of PD patients with GBA mutations and controls, we observed a significant GBA up-regulation during dopaminergic differentiation, paralleled by down-regulation of miR-22-3p. Our results describe the first microRNA controlling GBA and suggest that the GBAP1 non-coding RNA functions as a GBA ceRNA. [less ▲]

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See detailImpulsivity influences betting under stress in laboratory gambling
Canale, Natale; Rubaltelli, Enrico; Vieno, Alessio et al

in Scientific Reports (2017), 7

Although recent research suggests that acute stress influences subsequent decision-making under ambiguity, less is known about the role of personality variables in this relationship. This study tested ... [more ▼]

Although recent research suggests that acute stress influences subsequent decision-making under ambiguity, less is known about the role of personality variables in this relationship. This study tested whether impulsivity traits and acute stress differentially influence the way in which a prior feedback is incorporated into further decisions involving ambiguity. Sixty college students (50% male; aged 18–25 years) were randomly assigned to a stress versus a non-stress condition before completing a laboratory gambling task. The results revealed that independently of the stress condition, subjects behaved as if the odds of winning increase after a single loss. Additionally, stress effects varied as a function of impulsivity traits. Individuals who lacked perseverance (i.e., had difficulty focusing on a difficult or boring task) gambled more after experiencing a loss in the stress condition than did those in the control condition. The present study supports that impulsivity traits can explain the differential effect of stress on the relationship between prior feedback and choices made under ambiguity [less ▲]

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See detailCorrelates of social exclusion in social anxiety Disorder: An fMRI study
Heeren, Alexandre; Dricot, Laurence; Billieux, Joël UL et al

in Scientific Reports (2017), 7

Cognitive models posit that social anxiety disorder (SAD) is maintained by biased informationprocessing vis-à-vis threat of social exclusion. However, uncertainty still abounds regarding the very nature ... [more ▼]

Cognitive models posit that social anxiety disorder (SAD) is maintained by biased informationprocessing vis-à-vis threat of social exclusion. However, uncertainty still abounds regarding the very nature of this sensitivity to social exclusion in SAD. Especially, brain alterations related to social exclusion have not been explored in SAD. Our primary purpose was thus to determine both the selfreport and neural correlates of social exclusion in this population. 23 patients with SAD and 23 matched nonanxious controls played a virtual game (“Cyberball”) during fMRI recording. Participants were frst included by other players, then excluded, and fnally re-included. At the behavioral level, patients with SAD exhibited signifcantly higher levels of social exclusion feelings than nonanxious controls. At the brain level, patients with SAD exhibited signifcantly higher activation within the left inferior frontal gyrus relative to nonanxious controls during the re-inclusion phase. Moreover, self-report of social exclusion correlates with the activity of this cluster among individuals qualifying for SAD diagnosis. Our pattern of fndings lends strong support to the notion that SAD may be better portrayed by a poor ability to recover following social exclusion than during social exclusion per se. These fndings value social neuroscience as an innovative procedure to gain new insight into the underlying mechanisms of SAD. [less ▲]

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See detailAnalysis of the dynamic co-expression network of heart regeneration in the zebrafish
Rodius, Sophie; Androsova, Ganna UL; Götz, Lou et al

in Scientific Reports (2016), 6

The zebrafish has the capacity to regenerate its heart after severe injury. While the function of a few genes during this process has been studied, we are far from fully understanding how genes interact ... [more ▼]

The zebrafish has the capacity to regenerate its heart after severe injury. While the function of a few genes during this process has been studied, we are far from fully understanding how genes interact to coordinate heart regeneration. To enable systematic insights into this phenomenon, we generated and integrated a dynamic co-expression network of heart regeneration in the zebrafish and linked systems-level properties to the underlying molecular events. Across multiple post-injury time points, the network displays topological attributes of biological relevance. We show that regeneration steps are mediated by modules of transcriptionally coordinated genes, and by genes acting as network hubs. We also established direct associations between hubs and validated drivers of heart regeneration with murine and human orthologs. The resulting models and interactive analysis tools are available at http://infused.vital-it.ch. Using a worked example, we demonstrate the usefulness of this unique open resource for hypothesis generation and in silico screening for genes involved in heart regeneration. [less ▲]

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See detailThe topological Anderson insulator phase in the Kane-Mele model
Orth, Christoph; Sekera, Tibor; Bruder, Christoph et al

in Scientific Reports (2016), 6

It has been proposed that adding disorder to a topologically trivial mercury telluride/cadmium telluride (HgTe/CdTe) quantum well can induce a transition to a topologically nontrivial state. The resulting ... [more ▼]

It has been proposed that adding disorder to a topologically trivial mercury telluride/cadmium telluride (HgTe/CdTe) quantum well can induce a transition to a topologically nontrivial state. The resulting state was termed topological Anderson insulator and was found in computer simulations of the Bernevig-Hughes-Zhang model. Here, we show that the topological Anderson insulator is a more universal phenomenon and also appears in the Kane-Mele model of topological insulators on a honeycomb lattice. We numerically investigate the interplay of the relevant parameters, and establish the parameter range in which the topological Anderson insulator exists. A staggered sublattice potential turns out to be a necessary condition for the transition to the topological Anderson insulator. For weak enough disorder, a calculation based on the lowest-order Born approximation reproduces quantitatively the numerical data. Our results thus considerably increase the number of candidate materials for the topological Anderson insulator phase. [less ▲]

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