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

in Scientific Reports (2019)

Autophagic processes play a central role in cellular homeostasis. In pathological conditions, the flow of autophagy can be affected at multiple and distinct steps of the pathway. Current analyses tools do ... [more ▼]

Autophagic processes play a central role in cellular homeostasis. In pathological conditions, the flow of autophagy can be affected at multiple and distinct steps of the pathway. Current analyses tools do not deliver the required detail for dissecting pathway intermediates. The development of new tools to analyze autophagic processes qualitatively and quantitatively in a more straightforward manner is required. Defining all autophagy pathway intermediates in a high-throughput manner is technologically challenging and has not been addressed yet. Here, we overcome those requirements and limitations by the developed of stable autophagy and mitophagy reporter-iPSC and the establishment of a novel high-throughput phenotyping platform utilizing automated high-content image analysis to assess autophagy and mitophagy pathway intermediates. [less ▲]

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See detailA new class of protein biomarkers based on subcellular distribution: application to a mouse liver cancer model.
Sajic, Tatjana; Ciuffa, Rodolfo; Lemos, Vera et al

in Scientific reports (2019), 9(1), 6913

To-date, most proteomic studies aimed at discovering tissue-based cancer biomarkers have compared the quantity of selected proteins between case and control groups. However, proteins generally function in ... [more ▼]

To-date, most proteomic studies aimed at discovering tissue-based cancer biomarkers have compared the quantity of selected proteins between case and control groups. However, proteins generally function in association with other proteins to form modules localized in particular subcellular compartments in specialized cell types and tissues. Sub-cellular mislocalization of proteins has in fact been detected as a key feature in a variety of cancer cells. Here, we describe a strategy for tissue-biomarker detection based on a mitochondrial fold enrichment (mtFE) score, which is sensitive to protein abundance changes as well as changes in subcellular distribution between mitochondria and cytosol. The mtFE score integrates protein abundance data from total cellular lysates and mitochondria-enriched fractions, and provides novel information for the classification of cancer samples that is not necessarily apparent from conventional abundance measurements alone. We apply this new strategy to a panel of wild-type and mutant mice with a liver-specific gene deletion of Liver receptor homolog 1 (Lrh-1(hep-/-)), with both lines containing control individuals as well as individuals with liver cancer induced by diethylnitrosamine (DEN). Lrh-1 gene deletion attenuates cancer cell metabolism in hepatocytes through mitochondrial glutamine processing. We show that proteome changes based on mtFE scores outperform protein abundance measurements in discriminating DEN-induced liver cancer from healthy liver tissue, and are uniquely robust against genetic perturbation. We validate the capacity of selected proteins with informative mtFE scores to indicate hepatic malignant changes in two independent mouse models of hepatocellular carcinoma (HCC), thus demonstrating the robustness of this new approach to biomarker research. Overall, the method provides a novel, sensitive approach to cancer biomarker discovery that considers contextual information of tested proteins. [less ▲]

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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 detailEmotion-related impulsivity moderates the cognitive interference effect of smartphone availability on working memory.
Canale, Natale; Vieno, Alessio; Doro, Mattia et al

in Scientific reports (2019), 9(1), 18519

Although recent studies suggest that the mere presence of a smartphone might negatively impact on working memory capacity, fluid intelligence, and attentional processes, less is known about the individual ... [more ▼]

Although recent studies suggest that the mere presence of a smartphone might negatively impact on working memory capacity, fluid intelligence, and attentional processes, less is known about the individual differences that are liable to moderate this cognitive interference effect. This study tested whether individual differences in emotion-related impulsivity traits (positive urgency and negative urgency) moderate the effect of smartphone availability on cognitive performance. We designed an experiment in which 132 college students (age 18-25 years) completed a laboratory task that assessed visual working memory capacity in three different conditions: two conditions differing in terms of smartphone availability (smartphone turned off and visible, smartphone in silent mode and visible) and a condition in which the smartphone was not available and was replaced by a calculator (control condition). Participants also completed self-reports that assessed their thoughts after the task performance, positive/negative urgency, and problematic smartphone use. The results showed that participants with higher positive urgency presented increased cognitive interference (reflected by poorer task performance) in the "silent-mode smartphone" condition compared with participants in the "turned-off smartphone" condition. The present study provides new insights into the psychological factors that explain how smartphone availability is liable to interfere with high-level cognitive processes. [less ▲]

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See detailCross-disease analysis of Alzheimer’s disease and type-2 Diabetes highlights the role of autophagy in the pathophysiology of two highly comorbid diseases
Caberlotto, Laura; Nguyen, Thanh-Phuong UL; Lauria, Mario et al

in Scientific Reports (2019), 9(1), 3965

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See detailMicrobiota alter metabolism and mediate neurodevelopmental toxicity of 17β-estradiol
Catron, Tara R.; Swank, Adam; Wehmas, Leah C. et al

in Scientific Reports (2019), 9(1), 7064

Estrogenic chemicals are widespread environmental contaminants associated with diverse health and ecological effects. During early vertebrate development, estrogen receptor signaling is critical for many ... [more ▼]

Estrogenic chemicals are widespread environmental contaminants associated with diverse health and ecological effects. During early vertebrate development, estrogen receptor signaling is critical for many different physiologic responses, including nervous system function. Recently, host-associated microbiota have been shown to influence neurodevelopment. Here, we hypothesized that microbiota may biotransform exogenous 17-βestradiol (E2) and modify E2 effects on swimming behavior. Colonized zebrafish were continuously exposed to non-teratogenic E2 concentrations from 1 to 10 days post-fertilization (dpf). Changes in microbial composition and predicted metagenomic function were evaluated. Locomotor activity was assessed in colonized and axenic (microbe-free) zebrafish exposed to E2 using a standard light/dark behavioral assay. Zebrafish tissue was collected for chemistry analyses. While E2 exposure did not alter microbial composition or putative function, colonized E2-exposed larvae showed reduced locomotor activity in the light, in contrast to axenic E2-exposed larvae, which exhibited normal behavior. Measured E2 concentrations were significantly higher in axenic relative to colonized zebrafish. Integrated peak area for putative sulfonated and glucuronidated E2 metabolites showed a similar trend. These data demonstrate that E2 locomotor effects in the light phase are dependent on the presence of microbiota and suggest that microbiota influence chemical E2 toxicokinetics. More broadly, this work supports the concept that microbial colonization status may influence chemical toxicity. [less ▲]

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See detailMitochondrial morphology provides a mechanism for energy buffering at synapses.
Garcia, Guadalupe Clara UL; Bartol, Thomas M.; Phan, Sébastien et al

in Scientific reports (2019), 9

Mitochondria as the main energy suppliers of eukaryotic cells are highly dynamic organelles that fuse, divide and are transported along the cytoskeleton to ensure cellular energy homeostasis. While these ... [more ▼]

Mitochondria as the main energy suppliers of eukaryotic cells are highly dynamic organelles that fuse, divide and are transported along the cytoskeleton to ensure cellular energy homeostasis. While these processes are well established, substantial evidence indicates that the internal structure is also highly variable in dependence on metabolic conditions. However, a quantitative mechanistic understanding of how mitochondrial morphology affects energetic states is still elusive. To address this question, we here present an agent-based multiscale model that integrates three-dimensional morphologies from electron microscopy tomography with the molecular dynamics of the main ATP producing components. We apply our modeling approach to mitochondria at the synapse which is the largest energy consumer within the brain. Interestingly, comparing the spatiotemporal simulations with a corresponding space-independent approach, we find minor spatial effects when the system relaxes toward equilibrium but a qualitative difference in fluctuating environments. These results suggest that internal mitochondrial morphology is not only optimized for ATP production but also provides a mechanism for energy buffering and may represent a mechanism for cellular robustness. IM [less ▲]

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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 detailHigh surface recombination velocity limits Quasi-Fermi level splitting in kesterite absorbers
Redinger, Alex UL; Unold, Thomas

in Scientific Reports (2018)

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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 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)

Detailed reference viewed: 201 (20 UL)