No abstract

Histone deacetylase (HDAC) inhibitors have been exploited for years to improve recombinant protein expression in mammalian production cells. However, global HDAC inhibition is associated with negative effects on various cellular processes. microRNAs (miRNAs) have been shown to regulate gene expression in almost all eukaryotic cell types by controlling entire cellular pathways. Since miRNAs recently have gained much attention as next-generation cell engineering tool to improve Chinese hamster ovary (CHO) cell factories, we were interested if miRNAs are able to specifically repress HDAC expression in CHO cells to circumvent limitations of unspecific HDAC inhibition. We discovered a novel miRNA in CHO cells, miR-2861, which was shown to enhance productivity in various recombinant CHO cell lines. Furthermore, we demonstrate that miR-2861 might post-transcriptionally regulate HDAC5 in CHO cells. Intriguingly, siRNA-mediated HDAC5 suppression could be demonstrated to phenocopy pro-productive effects of miR-2861 in CHO cells. This supports the notion that miRNA-induced inhibition of HDAC5 may contribute to productivity enhancing effects of miR-2861. Furthermore, since product quality is fundamental to safety and functionality of biologics, we examined the effect of HDAC inhibition on critical product quality attributes. In contrast to unspecific HDAC inhibition using VPA, enforced expression of miR-2861 did not negatively influence antibody aggregation or N-glycosylation. Our findings highlight the superiority of miRNA-mediated inhibition of specific HDACs and present miR-2861 as novel cell engineering tool for improving CHO manufacturing cells.

The optical properties of pulsed laser deposited highly crystalline SrMoO3 thin films were investigated. Due to their low resistivity below 30 μΩ cm, thin films of SrMoO3 are candidates for transparent conductor applications. The transparency of SrMoO3 extends into the ultraviolet range to about 300 nm. In this range, SrMoO3 has a higher transparency at similar sheet resistance as compared to alternative oxide or metallic materials. Density functional theory shows that electron-electron correlation effects are small in SrMoO3 as compared to other low-resistivity transition metal oxides and predicts the optical properties in good agreement with experiment.

Structure and photostimulated luminescent properties of Eu-doped M 2 Ba X 4 ( M = Cs , Rb; X = Br , Cl) CsBr: Eu 2+ has recently been investigated as a photostimulable x-ray storage phosphor with great potential for application in high-resolution image plates. In a recent paper Hackenschmied et al. ͓J. Appl. Phys. 93, 5109 ͑2003͔͒ suggested that segregations of CsEuBr 3 or Cs 4 EuBr 6 formed within CsBr: Eu 2+ during annealing are responsible for an increase in the photostimulated luminescence ͑PSL͒ yield. In this work single crystals of CsEuBr 3 were prepared by a one step synthesis and identified by x-ray diffraction ͑XRD͒ analysis as single phase perovskites. It was concluded that, after preparation, CsEuBr 3 degrades in normal atmosphere into at least two phases, one of which is the orthorhombic structure of Cs 2 EuBr 5 · 10H 2 O. The XRD powder diffraction pattern of this compound is very similar to that of the segregations observed within CsBr: Eu 2+ and reported by Hackenschmied et al. However, the increased PSL yield in CsBr: Eu 2+ after annealing cannot be due to the segregations, because the trivalent nature of the europium in the segregations renders them PSL inactive.