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Transcriptional activation by c-Myc through specific E box elements is thought to be essential for its biological role. However, c-MycS is unable to activate transcription through these elements and yet retains the ability to stimulate proliferation, induce anchorage-independent growth, and induce apoptosis. In addition, c-MycS retains the ability to repress transcription of several specific promoters. Furthermore, c-MycS can rescue the cmyc null phenotype in fibroblasts with homozygous deletion of c-myc. Taken together, our data argue against the paradigm that all of the biological functions of c-Myc are mediated by transcriptional activation of specific target genes through E box elements.

Capacitive deionization (CDI) is a competent water desalination technique offering an appropriate route to obtain clean water. However, a rational designed structure of the electrode materials is essentially required for achieving high CDI performance. Here, a novel sponge‐templated strategy is developed for the first time to prepare graphene sheets with high specific surface area and suitable pore size distribution. Sponge is used as the support of graphene oxide to prevent the restack of graphene sheets, as well as to suppress the agglomerate during the annealing process. Importantly, the as‐fabricated graphene sheets possess high specific surface area of 305 m2 g−1 and wide pore size distribution. Ultrahigh CDI performance, a remarkable electrosorptive capacity of 4.95 mg g−1, and siginificant desorption rate of 25 min, is achieved with the sponge‐templated prepared graphene electrodes. This work provides an effective solution for the synthesis of rational graphene architectures for general applications in CDI, energy storage and conversion.

Mutations resulting in progranulin haploinsufficiency cause disease in patients with a subset of frontotemporal lobar degeneration; however, the biological functions of progranulin in the brain remain unknown. To address this subject, the present study initially assessed changes in gene expression and cytokine secretion in rat primary cortical neurons treated with progranulin. Molecular pathways enriched in the progranulin gene set included cell adhesion and cell motility pathways and pathways involved in growth and development. Secretion of cytokines and several chemokines linked to chemoattraction but not inflammation were also increased from progranulin-treated primary neurons. Therefore, whether progranulin is involved in recruitment of immune cells in the brain was investigated. Localized lentiviral expression of progranulin in C57BL/6 mice resulted in an increase of Iba1-positive microglia around the injection site. Moreover, progranulin alone was sufficient to promote migration of primary mouse microglia in vitro. Primary microglia and C4B8 cells demonstrated more endocytosis of amyloid β1-42 when treated with progranulin. These data demonstrate that progranulin acts as a chemoattractant in the brain to recruit or activate microglia and can increase endocytosis of extracellular peptides such as amyloid β.

Graphene-based materials have been widely used as electrode materials of supercapacitors. However, the intrinsic properties related to the capacitance of graphene-based materials essentially need to be clarified. In this work, we have prepared reduced graphene oxide (RGO) through a simple chemical reduction strategy by using hydrazine hydrate as the reducing reagent. The different reduction levels of graphene sheets were successfully realized by controlling the chemical reduction time, and the surface state and density of the functional group were precisely adjusted. We investigated the electrochemical performance of the as-prepared RGO electrode materials. A time dependence of the specific capacitance for the as-prepared RGO electrode was observed. Graphene oxide reduced by hydrazine hydrate at 95 °C for 60 min exhibited the highest weight specific capacitance. The RGO samples were systematically characterized with Fourier transform infrared (FTIR) spectra, X-ray photoelectron spectroscopy (XPS), and Raman measurements. We conclude that the oxygen-containing groups, electrical conductivity, density of defects, and carbon electronic state play substantial roles in deciding the specific capacitance of reduced graphene oxide.

Electrochemical post-treatment of ultrathin carbon layer coated cobalt nanoparticles generates a novel electrocatalyst, affording a small overpotential of 333 mV at a current density of 10 mA cm(-2) and a small Tafel slope of ∼58 mV per decade.

The interferon-inducible double-stranded-RNA(dsRNA)-dependent protein kinase PKR has been implicated in both the antiviral and cell growth-regulatory effects of the interferons. Over-expression of the wild-type form of this protein inhibits cell proliferation, whereas over-expression of inactive mutant forms transforms cells to a tumourigenic phenotype. It has been suggested that mutant PKR exerts a dominant negative effect on the activity of the wild-type protein lunase. We have investigated this possibility using the rabbit reticulocyte cell-free translation system in which protein synthesis is inhibited by dsRNA due to activation of PKR and phosphorylation of initiation factor eIF-2. Addition of a highly purified inactive PKR mutant, synthesised in a baculovirus-infected insect cell system, rescues protein synthesis from inhibition by low concentrations of dsRNA in a dose-dependent manner. The PKR mutant has no effect on protein synthesis in the absence of dsRNA or in the presence of another inhibitory protein kinase, the haem-controlled repressor. Inhibition of translation can be re-established in the presence of the mutant PKR by adding a higher concentration of dsRNA. These results suggest that inactive mutant PKR does exert a dominant negative effect on wild-type PKR and that this may be due to competition for dsRNA binding.The interferon-inducible double-stranded-(dsRNA)-activated protein kinase PKR, previously called DAI or p68, is believed to play a major role in the antiviral and antiproliferative effects of the interferons (IFN) [l]. Human PKR is a single polypeptide chain of M , approximately 62000 [21. The molecule consists of a protein kinase catalytic domain located in the C-terminal half, which contains conserved subdomains common to all protein kinases [3], and two dsRNAbinding domains situated in the N-terminal portion of the protein [4-61. PKR has two separate and well-characterized activities: in the presence of dsRNA the protein undergoes autophosphorylation and activation [7], and following such activation PKR phosphorylates the a subunit of polypeptide chain initiation factor eIF-2. Phosphorylation of eIF-2a leads to inhibition of protein synthesis by a well-established mechanism [8, 91.As well as being a mediator of the antiviral affects of IFN, PKR has now been identified as a potential tumoursuppressor-gene product (reviewed in [lo] nude mice [ l l , 121. The specific mutations used to inactivate the kinase were either a change of Lys to Arg at position 296 or deletion of amino-acid residues 361-366 between protein-kinase sub-domains V and VI of PKR. Cells transfected with wild-type kinase or with plasmid vector alone were nontumourigenic. Indeed those cells expressing the wild-type kinase exhibited inhibition of cell growth [12], behaviour which is consistent with recent evidence that the expression of human PKR in yeast cells results in poor growth [13]. These results suggest that over-expression of mutant forms of PKR leads to tumourigenesis due to interference with the active form ...