Influenza virosomes as vaccine adjuvant and carrier system.

The basic concept of virosomes is the controlled in vitro assembly of virus-like particles from purified components. The first generation of influenza virosomes developed two decades ago is successfully applied in licensed vaccines, providing a solid clinical safety and efficacy track record for the technology. In the meantime, a second generation of influenza virosomes has evolved as a carrier and adjuvant system, which is currently applied in preclinical and clinical stage vaccine candidates targeting various prophylactic and therapeutic indications.

Recent advances in mucosal immunization using virus-like particles.

Mucosal immunization offers the promises of eliciting a systemic and mucosal immune response, as well as enhanced patient compliance. Mucosal vaccination using defined antigens such as proteins and peptides requires delivery systems that combine good safety profiles with strong immunogenicity, which may be provided by virus-like particles (VLP). VLP are assembled from viral structural proteins and thus are devoid of any genetic material.

BRD7, a novel PBAF-specific SWI/SNF subunit, is required for target gene activation and repression in embryonic stem cells.

The composition of chromatin-remodeling complexes dictates how these enzymes control transcriptional programs and cellular identity. In the present study we investigated the composition of SWI/SNF complexes in embryonic stem cells (ESCs). In contrast to differentiated cells, ESCs have a biased incorporation of certain paralogous SWI/SNF subunits with low levels of BRM, BAF170, and ARID1B.

Remodeling plans for cellular specialization: unique styles for every room.

Chromatin-remodeling complexes are biochemically diverse, functionally selective machines that regulate crucial aspects of DNA metabolism, including transcription and chromatin assembly. These complexes modulate histone-DNA interactions to affect nucleosome repositioning and disassembly, and histone variant exchange, thereby generating compositionally specialized chromatin. Recent studies have revealed precise mechanisms by which specific remodelers control the transition from proliferating progenitors to committed cells through a highly synchronized switch in transcriptional programs.

Promoter-specific p53-dependent histone acetylation following DNA damage.

We have used chromatin immunoprecipitation (ChIP) to measure p53-dependent histone acetylation at the p21, MDM2, and PUMA promoters. The pattern of histone acetylation was different at each promoter. H3 and H4 acetylation increased at both the p21 and PUMA promoters in response to p53 activation, whereas there was only a minimal increase in H4 acetylation and no increase in H3 acetylation at the MDM2 promoter.

Regulation of p53 stability and function in HCT116 colon cancer cells.

We have used a lentiviral vector to stably express p53 at a physiological level in p53 knockout HCT116 cells. Cells transduced with wild type p53 responded to genotoxic stress by stabilizing p53 and expressing p53 target genes. The reconstituted cells underwent G(1) arrest or apoptosis appropriately depending on the type of stress, albeit less efficiently than parental wild type cells.

Cell type- and promoter-specific roles of Ser18 phosphorylation in regulating p53 responses.

Phosphorylation of mouse p53 at Ser18 occurs after DNA damage. To determine the physiological roles of this phosphorylation event in p53-dependent DNA damage responses, a Ser18 to Ala missense mutation was introduced into the germline of mice. Thymocytes and fibroblasts from the knock-in mice show reduced transactivation of many p53 target genes following DNA damage.