Activation of pluripotency genes in human fibroblast cells by a novel mRNA based approach

Background: Several methods have been used to induce somatic cells to re-enter the pluripotent state. Viral transduction of reprogramming genes yields higher efficiency but involves random insertions of viral sequences into the human genome. Although induced pluripotent stem (iPS) cells can be obtained with the removable PiggyBac transposon system or an episomal system, both approaches still use DNA constructs so that resulting cell lines need to be thoroughly analyzed to confirm they are free of harmful genetic modification. Thus a method to change cell fate without using DNA will be very useful in regenerative medicine. Methodology/Principal Findings: In this study, we synthesized mRNAs encoding OCT4, SOX2, cMYC, KLF4 and SV40 large T (LT) and electroporated them into human fibroblast cells. Upon transfection, fibroblasts expressed these factors at levels comparable to, or higher than those in human embryonic stem (ES) cells. Ectopically expressed OCT4 localized to the cell nucleus within 4 hours after mRNA introduction. Transfecting fibroblasts with a mixture of mRNAs encoding all five factors significantly increased the expression of endogenous OCT4, NANOG, DNMT3 beta, REX1 and SALL4. When such transfected fibroblasts were also exposed to several small molecules (valproic acid, BIX01294 and 5'-aza-2'-deoxycytidine) and cultured in human embryonic stem cell (ES) medium they formed small aggregates positive for alkaline phosphatase activity and OCT4 protein within 30 days. Conclusion/Significance: Our results demonstrate that mRNA transfection can be a useful approach to precisely control the protein expression level and short-term expression of reprogramming factors is sufficient to activate pluripotency genes in differentiated cells

Open-closed field algebras

We introduce the notions of open-closed field algebra and open-closed field algebra over a vertex operator algebra V. In the case that V satisfies certain finiteness and reductivity conditions, we show that an open-closed field algebra over V canonically gives an algebra over a \C-extension of the Swiss-cheese partial operad. We also give a tensor categorical formulation and categorical constructions of open-closed field algebras over V.Comment: 55 pages, largely revised, an old subsection is deleted, a few references are adde

Synchronisation of linear continuous multi-agent systems with switching topology and communication delay

A distributed dynamic output feedback control is designed by Scardovi and Sepulchre for the synchronization of a network of identical linear systems, known as agents in literature. The design is based on some mild conditions allowing switching topology. But it assumes that there is no time delay in signal transfer between the neighbouring agents. In this paper we extend their work to include known time delay in communications. Furthermore, our design has some special features: (a) the delay can be arbitrary and only need to be uniformly bounded by a constant, (b) the conditions that time delay should be the same and sufficiently small in some literature are not required here, and (c) no local buffer is required to store past data due to time-delay effect

Edge states of graphene bilayer strip

The electronic structure of the zig-zag bilayer strip is analyzed. The electronic spectra of the bilayer strip is computed. The dependence of the edge state band flatness on the bilayer width is found. The density of states at the Fermi level is analytically computed. It is shown that it has the singularity which depends on the width of the bilayer strip. There is also asymmetry in the density of states below and above the Fermi energy.Comment: 9 page