Expressed protein profile of a Tectomicrobium and other microbial symbionts in the marine sponge Aplysina aerophoba as evidenced by metaproteomics.

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 ▲]

SeesawPred: A Web Application for Predicting Cell-fate Determinants in Cell Differentiation

in Scientific Reports (2018)

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 ▲]

Helicobacter pylori targets mitochondrial import and components of mitochondrial DNA replication machinery through an alternative VacA-dependent and a VacA-independent mechanisms.

in Scientific reports (2017), 7(1), 15901

Targeting mitochondria is a powerful strategy for pathogens to subvert cell physiology and establish infection. Helicobacter pylori is a bacterial pathogen associated with gastric cancer development that ... [more ▼]

Targeting mitochondria is a powerful strategy for pathogens to subvert cell physiology and establish infection. Helicobacter pylori is a bacterial pathogen associated with gastric cancer development that is known to target mitochondria directly and exclusively through its pro-apoptotic and vacuolating cytotoxin VacA. By in vitro infection of gastric epithelial cells with wild-type and VacA-deficient H. pylori strains, treatment of cells with purified VacA proteins and infection of a mouse model, we show that H. pylori deregulates mitochondria by two novel mechanisms, both rather associated with host cell survival. First, early upon infection VacA induces transient increase of mitochondrial translocases and a dramatic accumulation of the mitochondrial DNA replication and maintenance factors POLG and TFAM. These events occur when VacA is not detected intracellularly, therefore do not require the direct interaction of the cytotoxin with the organelle, and are independent of the toxin vacuolating activity. In vivo, these alterations coincide with the evolution of gastric lesions towards severity. Second, H. pylori also induces VacA-independent alteration of mitochondrial replication and import components, suggesting the involvement of additional H. pylori activities in mitochondria-mediated effects. These data unveil two novel mitochondrial effectors in H. pylori-host interaction with links on gastric pathogenesis. [less ▲]

Impulsivity influences betting under stress in laboratory gambling

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 ▲]

Analysis of the dynamic co-expression network of heart regeneration in the zebrafish

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 ▲]

Single crystalline cylindrical nanowires – toward dense 3D arrays of magnetic vortices

in Scientific Reports (2016), 6