Live Intracellular Biorthogonal Imaging by Surface Enhanced Raman Spectroscopy using Alkyne-Silver Nanoparticles Clusters

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 ▲]

Opposite feedback from mTORC1 to H-ras and K-ras4B downstream of SREBP1

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 ▲]

Prediction of Chromatin Accessibility in Gene-Regulatory Regions from Transcriptomics Data

in Scientific Reports (2017)

Deliberate and Accidental Gas-Phase Alkali Doping of Chalcogenide Semiconductors: Cu(In,Ga)Se2

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 ▲]

The GBAP1 pseudogene acts as a ceRNA for the glucocerebrosidase gene GBA by sponging miR-22-3p.

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 ▲]

Correlates of social exclusion in social anxiety Disorder: An fMRI study

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 ▲]

Small-angle neutron scattering modeling of spin disorder in nanoparticles

in Scientific Reports (2017), 7

The topological Anderson insulator phase in the Kane-Mele model

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 ▲]

High-fidelity spherical cholesteric liquid crystal Bragg reflectors generating unclonable patterns for secure authentication

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 ▲]

Direct observation of polar tweed in LaAlO3

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 ▲]