UV-crosslinked Polymeric Materials for Encapsulation of ZnO Nanowires in Piezoelectric Fingerprint Sensors

The work presented here describes new UV-crosslinkable thin layer polymeric materials for the encapsulation of ZnO nanowires (NWs) in multi-NWs pressure based fingerprint sensors. Such innovative sensor is a novel technology for fingerprint capture developed within the PiezoMAT FP7 European project. The sensing principle is based on the piezoelectric property of ZnO NWs, on which a potential difference is generated when they undergo compression and/or bending forces. Since the pressure induced by the finger cannot be directly applied on the NWs, the deformation is applied through a polymeric material that aims at transferring forces from the finger onto the array of NWs without altering their integrity. Besides, since it is dedicated to be in direct contact with human finger or oil pollutants, the encapsulation layer must also exhibit chemical inertness, as well as hydrophobicity and oleophobicity

Chemoinformatic-guided engineering of polyketide synthases

Polyketide synthase (PKS) engineering is an attractive method to generate new molecules such as commodity, fine and specialty chemicals. A central challenge in PKS design is replacing a partially reductive module with a fully reductive module through a reductive loop exchange, thereby generating a saturated β-carbon. In this work, we sought to establish an engineering strategy for reductive loop exchanges based on chemoinformatics, a field traditionally used in drug discovery. We first introduced a set of donor reductive loops of diverse genetic origin and chemical substrate structures into the first extension module of the lipomycin PKS (LipPKS1). These results demonstrated that chemical similarity between the substrate of the donor loops and recipient LipPKS1 correlated with product titers. Consequently, we identified donor loops with substrates chemically similar to LipPKS1 for further reductive loop exchanges, and we observed a statistically significant correlation with production. Reductive loops with the highest chemical similarity resulted in production of branched, short-chain fatty acids reaching a titer of 165 mg/L in Streptomyces albus J1074. Collectively, our work formulizes a new chemoinformatic paradigm for de novo PKS biosynthesis which may accelerate the production of valuable bioproducts

Chemoinformatic-Guided Engineering of Polyketide Synthases.

Polyketide synthase (PKS) engineering is an attractive method to generate new molecules such as commodity, fine and specialty chemicals. A significant challenge is re-engineering a partially reductive PKS module to produce a saturated β-carbon through a reductive loop (RL) exchange. In this work, we sought to establish that chemoinformatics, a field traditionally used in drug discovery, offers a viable strategy for RL exchanges. We first introduced a set of donor RLs of diverse genetic origin and chemical substrates  into the first extension module of the lipomycin PKS (LipPKS1). Product titers of these engineered unimodular PKSs correlated with chemical structure similarity between the substrate of the donor RLs and recipient LipPKS1, reaching a titer of 165 mg/L of short-chain fatty acids produced by the host Streptomyces albus J1074. Expanding this method to larger intermediates that require bimodular communication, we introduced RLs of divergent chemosimilarity into LipPKS2 and determined triketide lactone production. Collectively, we observed a statistically significant correlation between atom pair chemosimilarity and production, establishing a new chemoinformatic method that may aid in the engineering of PKSs to produce desired, unnatural products

Inhibition of Hedgehog Signaling Decreases Proliferation and Clonogenicity of Human Mesenchymal Stem Cells

Human mesenchymal stem cells (hMSC) have the ability to differentiate into osteoblasts, adipocytes and chondrocytes. We have previously shown that hMSC were endowed with a basal level of Hedgehog signaling that decreased after differentiation of these cells. Since hMSC differentiation is associated with growth-arrest we investigated the function of Hh signaling on cell proliferation. Here, we show that inhibition of Hh signaling, using the classical inhibitor cyclopamine, or a siRNA directed against Gli-2, leads to a decrease in hMSC proliferation. This phenomenon is not linked to apoptosis but to a block of the cells in the G0/G1 phases of the cell cycle. At the molecular level, it is associated with an increase in the active form of pRB, and a decrease in cyclin A expression and MAP kinase phosphorylation. Inhibition of Hh signaling is also associated with a decrease in the ability of the cells to form clones. By contrast, inhibition of Hh signaling during hMSC proliferation does not affect their ability to differentiate. This study demonstrates that hMSC are endowed with a basal Hedgehog signaling activity that is necessary for efficient proliferation and clonogenicity of hMSC. This observation unravels an unexpected new function for Hedgehog signaling in the regulation of human mesenchymal stem cells and highlights the critical function of this morphogen in hMSC biology

UV-crosslinked polymeric materials for encapsulation of ZnO nanowires in piezoelectric fingerprint sensors

The work presented here describes new UV-crosslinkable thin layer polymeric materials for the encapsulation of ZnO nanowires (NWs) in multi-NWs pressure based fingerprint sensors. Such innovative sensor is a novel technology for fingerprint capture developed within the PiezoMAT FP7 European project. The sensing principle is based on the piezoelectric property of ZnO NWs, on which a potential difference is generated when they undergo compression and/or bending forces. Since the pressure induced by the finger cannot be directly applied on the NWs, the deformation is applied through a polymeric material that aims at transferring forces from the finger onto the array of NWs without altering their integrity. Besides, since it is dedicated to be in direct contact with human finger or oil pollutants, the encapsulation layer must also exhibit chemical inertness, as well as hydrophobicity and oleophobicity