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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 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 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 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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See detailSingle crystalline cylindrical nanowires – toward dense 3D arrays of magnetic vortices
Ivanov, Yurii P.; Chuvilin, Andrey; Gonzalez Vivas, Laura UL et al

in Scientific Reports (2016), 6

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See detailHigh-fidelity spherical cholesteric liquid crystal Bragg reflectors generating unclonable patterns for secure authentication
Geng, Yong UL; Noh, Junghyun UL; Drevensek-Olenik, Irena et al

in Scientific Reports (2016), 6(26840), 1-8

Monodisperse cholesteric liquid crystal microspheres exhibit spherically symmetric Bragg reflection, generating, via photonic cross communication, dynamically tuneable multi-coloured patterns. These ... [more ▼]

Monodisperse cholesteric liquid crystal microspheres exhibit spherically symmetric Bragg reflection, generating, via photonic cross communication, dynamically tuneable multi-coloured patterns. These patterns, uniquely defined by the particular sphere arrangement, could render cholesteric microspheres very useful in countless security applications, as tags to identify and authenticate their carriers, mainly physical objects or persons. However, the optical quality of the cholesteric droplets studied so far is unsatisfactory, especially after polymerisation, a step required for obtaining durable samples that can be used for object identification. We show that a transition from droplets to shells solves all key problems, giving rise to sharp patterns and excellent optical quality even after polymerisation, the polymerised shells sustaining considerable mechanical deformation. Moreover, we demonstrate that, counter to prior expectation, cross communication takes place even between non-identical shells. This opens additional communication channels that add significantly to the complexity and unique character of the generated patterns. [less ▲]

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See detailEnteric neurons from Parkinson's disease patients display ex vivo aberrations in mitochondrial structure.
Baumuratov, Aidos UL; Antony, Paul UL; Ostaszewski, Marek UL et al

in Scientific reports (2016), 6

Based on autopsy material mitochondrial dysfunction has been proposed being part of the pathophysiological cascade of Parkinson's disease (PD). However, in living patients, evidence for such dysfunction ... [more ▼]

Based on autopsy material mitochondrial dysfunction has been proposed being part of the pathophysiological cascade of Parkinson's disease (PD). However, in living patients, evidence for such dysfunction is scarce. As the disease presumably starts at the enteric level, we studied ganglionic and mitochondrial morphometrics of enteric neurons. We compared 65 ganglia from 11 PD patients without intestinal symptoms and 41 ganglia from 4 age-matched control subjects. We found that colon ganglia from PD patients had smaller volume, contained significantly more mitochondria per ganglion volume, and displayed a higher total mitochondrial mass relative to controls. This suggests involvement of mitochondrial dysfunction in PD at the enteric level. Moreover, in PD patients the mean mitochondrial volume declined in parallel with motor performance. Ganglionic shrinking was evident in the right but not in the left colon. In contrast, mitochondrial changes prevailed in the left colon suggesting that a compensatory increase in mitochondrial mass might counterbalance mitochondrial dysfunction in the left colon but not in the right colon. Reduction in ganglia volume and combined mitochondrial morphometrics had both predictive power to discriminate between PD patients and control subjects, suggesting that both parameters could be used for early discrimination between PD patients and healthy individuals. [less ▲]

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See detailLow energy electron imaging of domains and domain walls in magnesium-doped lithium niobate
Nataf, G. F.; Grysan, P.; Guennou, Mael UL et al

in SCIENTIFIC REPORTS (2016), 6

The understanding of domain structures, specifically domain walls currently attracts a significant attention in the field of (multi)-ferroic materials. In this article, we analyze contrast formation in ... [more ▼]

The understanding of domain structures, specifically domain walls currently attracts a significant attention in the field of (multi)-ferroic materials. In this article, we analyze contrast formation in full field electron microscopy applied to domains and domain walls in the uniaxial ferroelectric lithium niobate, which presents a large 3.8 eV band gap and for which conductive domain walls have been reported. We show that the transition from Mirror Electron Microscopy (MEM - electrons reflected) to Low Energy Electron Microscopy (LEEM - electrons backscattered) gives rise to a robust contrast between domains with upwards (P-up) and downwards (P-down) polarization, and provides a measure of the difference in surface potential between the domains. We demonstrate that out-of-focus conditions of imaging produce contrast inversion, due to image distortion induced by charged surfaces and also carry information on the polarization direction in the domains. Finally, we show that the intensity profile at domain walls provides experimental evidence for a local stray, lateral electric field. [less ▲]

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See detailDirect observation of polar tweed in LaAlO3
Salje, Ekhard K. H.; Alexe, Marin; Kustov, Sergey et al

in SCIENTIFIC REPORTS (2016), 6

Polar tweed was discovered in mechanically stressed LaAlO3. Local patches of strained material (diameter ca. 5 mu m) form interwoven patterns seen in birefringence images, Piezo-Force Microscopy (PFM) and ... [more ▼]

Polar tweed was discovered in mechanically stressed LaAlO3. Local patches of strained material (diameter ca. 5 mu m) form interwoven patterns seen in birefringence images, Piezo-Force Microscopy (PFM) and Resonant Piezoelectric Spectroscopy (RPS). PFM and RPS observations prove unequivocally that electrical polarity exists inside the tweed patterns of LaAlO3. The local piezoelectric effect varies greatly within the tweed patterns and reaches magnitudes similar to quartz. The patterns were mapped by the shift of the E-g soft-mode frequency by Raman spectroscopy. [less ▲]

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See detailMagnetic neutron scattering by magnetic vortices in thin submicron-sized soft ferromagnetic cylinders
Metlov, K.L.; Michels, Andreas UL

in Scientific Reports (2016), 6

Using analytical expressions for the magnetization textures of thin submicron-sized magnetic cylinders in vortex state, we derive closed-form algebraic expressions for the ensuing small-angle neutron ... [more ▼]

Using analytical expressions for the magnetization textures of thin submicron-sized magnetic cylinders in vortex state, we derive closed-form algebraic expressions for the ensuing small-angle neutron scattering (SANS) cross sections. Specifically, for the perpendicular and parallel scattering geometries, we have computed the cross sections for the case of small vortex-center displacements without formation of magnetic charges on the side faces of the cylinder. The results represent a significant qualitative and quantitative step forward in SANS-data analysis on isolated magnetic nanoparticle systems, which are commonly assumed to be homogeneously or stepwise-homogeneously magnetized. We suggest a way to extract the fine details of the magnetic vortex structure during the magnetization process from the SANS measurements in order to help resolving the long-standing question of the magnetic vortex displacement mode. [less ▲]

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See detailDiversity of key players in the microbial ecosystems of the human body.
Jordan, Ferenc; Lauria, Mario; Scotti, Marco et al

in Scientific reports (2015), 5

Coexisting bacteria form various microbial communities in human body parts. In these ecosystems they interact in various ways and the properties of the interaction network can be related to the stability ... [more ▼]

Coexisting bacteria form various microbial communities in human body parts. In these ecosystems they interact in various ways and the properties of the interaction network can be related to the stability and functional diversity of the local bacterial community. In this study, we analyze the interaction network among bacterial OTUs in 11 locations of the human body. These belong to two major groups. One is the digestive system and the other is the female genital tract. In each local ecosystem we determine the key species, both the ones being in key positions in the interaction network and the ones that dominate by frequency. Beyond identifying the key players and discussing their biological relevance, we also quantify and compare the properties of the 11 networks. The interaction networks of the female genital system and the digestive system show totally different architecture. Both the topological properties and the identity of the key groups differ. Key groups represent four phyla of prokaryotes. Some groups appear in key positions in several locations, while others are assigned only to a single body part. The key groups of the digestive and the genital tracts are totally different. [less ▲]

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See detailNovel drug target identification for the treatment of dementia using multi-relational association mining
Nguyen, Thanh-Phuong UL; Priami, Corrado; Caberlotto, Laura

in Scientific Reports (2015), 5

Dementia is a neurodegenerative condition of the brain in which there is a progressive and permanent loss of cognitive and mental performance. Despite the fact that the number of people with dementia ... [more ▼]

Dementia is a neurodegenerative condition of the brain in which there is a progressive and permanent loss of cognitive and mental performance. Despite the fact that the number of people with dementia worldwide is steadily increasing and regardless of the advances in the molecular characterization of the disease, current medical treatments for dementia are purely symptomatic and hardly effective. We present a novel multi-relational association mining method that integrates the huge amount of scientific data accumulated in recent years to predict potential novel targets for innovative therapeutic treatment of dementia. Owing to the ability of processing large volumes of heterogeneous data, our method achieves a high performance and predicts numerous drug targets including several serine threonine kinase and a G-protein coupled receptor. The predicted drug targets are mainly functionally related to metabolism, cell surface receptor signaling pathways, immune response, apoptosis, and long-term memory. Among the highly represented kinase family and among the G-protein coupled receptors, DLG4 (PSD-95), and the bradikynin receptor 2 are highlighted also for their proposed role in memory and cognition, as described in previous studies. These novel putative targets hold promises for the development of novel therapeutic approaches for the treatment of dementia. [less ▲]

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See detailTRIM32 modulates pluripotency entry and exit by directly regulating Oct4 stability
Bahnassawy, Lamia’a; Perumal, Thanneer; Gonzalez Cano, Laura UL et al

in Scientific Reports (2015)

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See detailLow-bias phosphopeptide enrichment from scarce samples using plastic antibodies
Chen, Jing; Shinde, Sudhirkumar; Koch, Markus-Hermann et al

in Scientific reports (2015), 5

Phosphospecific enrichment techniques and mass spectrometry (MS) are essential tools for comprehending the cellular phosphoproteome. Here, we report a fast and simple approach for low sequence-bias ... [more ▼]

Phosphospecific enrichment techniques and mass spectrometry (MS) are essential tools for comprehending the cellular phosphoproteome. Here, we report a fast and simple approach for low sequence-bias phosphoserine (pS) peptide capture and enrichment that is compatible with low biological or clinical sample input. The approach exploits molecularly imprinted polymers (MIPs, "plastic antibodies") featuring tight neutral binding sites for pS or pY that are capable of cross-reacting with phosphopeptides of protein proteolytic digests. The versatility of the resulting method was demonstrated with small samples of whole-cell lysate from human embryonic kidney (HEK) 293T cells, human neuroblastoma SH-SY5Y cells, mouse brain or human cerebrospinal fluid (CSF). Following pre-fractionation of trypsinized proteins by strong cation exchange (SCX) chromatography, pS-MIP enrichment led to the identification of 924 phosphopeptides in the HEK 293T whole-cell lysate, exceeding the number identified by TiO2-based enrichment (230). Moreover, the phosphopeptides were extracted with low sequence bias and showed no evidence for the characteristic preference of TiO2 for acidic amino acids (aspartic and glutamic acid). Applying the method to human CSF led to the discovery of 47 phosphopeptides belonging to 24 proteins and revealed three previously unknown phosphorylation sites. [less ▲]

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See detailA novel immunofluorescent assay to investigate oxidative phosphorylation deficiency in mitochondrial myopathy: understanding mechanisms and improving diagnosis.
Rocha, Mariana C.; Grady, John P.; Grünewald, Anne UL et al

in Scientific reports (2015), 5

Oxidative phosphorylation defects in human tissues are often challenging to quantify due to a mosaic pattern of deficiency. Biochemical assays are difficult to interpret due to the varying enzyme ... [more ▼]

Oxidative phosphorylation defects in human tissues are often challenging to quantify due to a mosaic pattern of deficiency. Biochemical assays are difficult to interpret due to the varying enzyme deficiency levels found in individual cells. Histochemical analysis allows semi-quantitative assessment of complex II and complex IV activities, but there is no validated histochemical assay to assess complex I activity which is frequently affected in mitochondrial pathology. To help improve the diagnosis of mitochondrial disease and to study the mechanisms underlying mitochondrial abnormalities in disease, we have developed a quadruple immunofluorescent technique enabling the quantification of key respiratory chain subunits of complexes I and IV, together with an indicator of mitochondrial mass and a cell membrane marker. This assay gives precise and objective quantification of protein abundance in large numbers of individual muscle fibres. By assessing muscle biopsies from subjects with a range of different mitochondrial genetic defects we have demonstrated that specific genotypes exhibit distinct biochemical signatures in muscle, providing evidence for the diagnostic use of the technique, as well as insight into the underlying molecular pathology. Stringent testing for reproducibility and sensitivity confirms the potential value of the technique for mechanistic studies of disease and in the evaluation of therapeutic approaches. [less ▲]

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