Coherent coupling of single molecules to on-chip ring resonators

We report on cryogenic coupling of organic molecules to ring microresonators obtained by looping sub-wavelength waveguides (nanoguides). We discuss fabrication and characterization of the chip-based nanophotonic elements which yield resonator finesse in the order of 20 when covered by molecular crystals. Our observed extinction dips from single molecules reach 22%, consistent with the expected Purcell enhancements up to 11 folds. Future efforts will aim at efficient coupling of a handful of molecules via their interaction with a ring microresonator mode, setting the ground for the realization of quantum optical cooperative effects

On-chip interference of scattering from two individual molecules in plastic

Integrated photonic circuits offer a promising route for studying coherent cooperative effects of a controlled collection of quantum emitters. However, spectral inhomogeneities, decoherence and material incompatibilities in the solid state make this a nontrivial task. Here, we demonstrate efficient coupling of a pair of organic molecules embedded in a plastic film to a TiO$_2$ microdisc resonator on a glass chip. Moreover, we tune the resonance frequencies of the molecules with respect to that of the microresonator by employing nanofabricated electrodes. For two molecules separated by a distance of about 8$\,\mu$m and an optical phase difference of about $\pi/2$, we report on a large collective extinction of the incident light in the forward direction and the destructive interference of its scattering in the backward direction. Our work sets the ground for the coherent coupling of several molecules via a common mode and the realization of polymer-based hybrid quantum photonic circuits

The hepatitis C viral nonstructural protein 5A stabilizes growth-regulatory human transcripts

Numerous mammalian proto-oncogene and other growth-regulatory transcripts are upregulated in malignancy due to abnormal mRNA stabilization. In hepatoma cells expressing a hepatitis C virus (HCV) subgenomic replicon, we found that the viral nonstructural protein 5A (NS5A), a protein known to bind to viral RNA, also bound specifically to human cellular transcripts that encode regulators of cell growth and apoptosis, and this binding correlated with transcript stabilization. An important subset of human NS5A-target transcripts contained GU-rich elements, sequences known to destabilize mRNA. We found that NS5A bound to GU-rich elements in vitro and in cells. Mutation of the NS5A zinc finger abrogated its GU-rich element-binding and mRNA stabilizing activities. Overall, we identified a molecular mechanism whereby HCV manipulates host gene expression by stabilizing host transcripts in a manner that would promote growth and prevent death of virus-infected cells, allowing the virus to establish chronic infection and lead to the development of hepatocellular carcinoma. © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research

No Effect of Microgravity and Simulated Mars Gravity on Final Bacterial Cell Concentrations on the International Space Station: Applications to Space Bioproduction

Microorganisms perform countless tasks on Earth and they are expected to be essential for human space exploration. Despite the interest in the responses of bacteria to space conditions, the findings on the effects of microgravity have been contradictory, while the effects of Martian gravity are nearly unknown. We performed the ESA BioRock experiment on the International Space Station to study microbe-mineral interactions in microgravity, simulated Mars gravity and simulated Earth gravity, as well as in ground gravity controls, with three bacterial species: Sphingomonas desiccabilis, Bacillus subtilis, and Cupriavidus metallidurans. To our knowledge, this was the first experiment to study simulated Martian gravity on bacteria using a space platform. Here, we tested the hypothesis that different gravity regimens can influence the final cell concentrations achieved after a multi-week period in space. Despite the different sedimentation rates predicted, we found no significant differences in final cell counts and optical densities between the three gravity regimens on the ISS. This suggests that possible gravityrelated effects on bacterial growth were overcome by the end of the experiment. The results indicate that microbial-supported bioproduction and life support systems can be effectively performed in space (e.g., Mars), as on Earth

p21WAF1/CIP1 Upregulation through the Stress Granule-Associated Protein CUGBP1 Confers Resistance to Bortezomib-Mediated Apoptosis

p21(WAF1/CIP1) is a well known cyclin-dependent kinase inhibitor induced by various stress stimuli. Depending on the stress applied, p21 upregulation can either promote apoptosis or prevent against apoptotic injury. The stress-mediated induction of p21 involves not only its transcriptional activation but also its posttranscriptional regulation, mainly through stabilization of p21 mRNA levels. We have previously reported that the proteasome inhibitor MG132 induces the stabilization of p21 mRNA, which correlates with the formation of cytoplasmic RNA stress granules. The mechanism underlying p21 mRNA stabilization, however, remains unknown.We identified the stress granules component CUGBP1 as a factor required for p21 mRNA stabilization following treatment with bortezomib ( =  PS-341/Velcade). This peptide boronate inhibitor of the 26S proteasome is very efficient for the treatment of myelomas and other hematological tumors. However, solid tumors are sometimes refractory to bortezomib treatment. We found that depleting CUGBP1 in cancer cells prevents bortezomib-mediated p21 upregulation. FISH experiments combined to mRNA stability assays show that this effect is largely due to a mistargeting of p21 mRNA in stress granules leading to its degradation. Altering the expression of p21 itself, either by depleting CUGBP1 or p21, promotes bortezomib-mediated apoptosis.We propose that one key mechanism by which apoptosis is inhibited upon treatment with chemotherapeutic drugs might involve upregulation of the p21 protein through CUGBP1