Safety and Immunogenicity of a Novel Recombinant Subunit Respiratory Syncytial Virus Vaccine (BBG2Na) in Healthy Young Adults

A novel recombinant respiratory syncytial virus (RSV) subunit vaccine, designated BBG2Na, was administered to 108 healthy adults randomly assigned to receive 10, 100, or 300 μg of BBG2Na in aluminum phosphate or saline placebo. Each subject received 1, 2, or 3 intramuscular injections of the assigned dose at monthly intervals. Local and systemic reactions were mild, and no evidence of harmful properties of BBG2Na was reported. The highest ELISA and virus-neutralizing (VN) antibody responses were evident in the 100- and 300-μg groups; second or third injections provided no significant boosts against RSV-derived antigens. BBG2Na induced ⩾2-fold and ⩾4-fold increases in G2Na-specific ELISA units in up to 100% and 57% of subjects, respectively; corresponding RSV-A–specific responses were 89% and 67%. Furthermore, up to 71% of subjects had ⩾2-fold VN titer increases. Antibody responses to 2 murine lung protective epitopes were also highly boosted after vaccination. Therefore, BBG2Na is safe, well tolerated, and highly immunogenic in RSV-seropositive adults

Identification of the p28 subunit of eukaryotic initiation factor 3(eIF3k) as a new interaction partner of cyclin D3.

Cyclin D3 is found to play a crucial role not only in progression through the G1 phase as a regulatory subunit of cyclin-dependent kinase 4 (CDK 4) and CDK 6, but also in many other aspects such as cell cycle, cell differentiation, transcriptional regulation and apoptosis. In this work, we screened a human fetal liver cDNA library using human cyclin D3 as bait and identified human eukaryotic initiation factor 3 p28 protein (eIF3k) as a partner of cyclin D3. The association of cyclin D3 with eIF3k was further confirmed by in vitro binding assay, in vivo coimmunoprecipitation, and confocal microscopic analysis. We found that cyclin D3 specifically interacted with eIF3k through its C-terminal domain. Immunofluorescence experiments showed that eIF3k distributed both in nucleus and cytoplasm and colocalized with cyclin D3. In addition, the cellular translation activity in HeLa cells was upregulated by cyclin D3 overexpression and the mRNA levels are constant. These data provide a new clue to our understanding of the cellular function of cyclin D3.

The component masses of the cataclysmic variable V347 Puppis

We present time-resolved spectroscopy and photometry of the double-lined eclipsing cataclysmic variable V347 Pup ( = LB 1800). There is evidence of irradiation on the inner hemisphere of the secondary star, which we correct for using a model to give a secondary-star radial velocity of K R = 198 +/- 5 km s(-1). The rotational velocity of the secondary star in V347 Pup is found to be v sin i = 131 +/- 5 km s(-1) and the system inclination is i = 84degrees.0 +/- 2degrees.3. From these parameters we obtain masses of M-1 = 0.63 +/- 0.04 M for the white dwarf primary and M-2 = 0.52 +/- 0.06 M for the M0.5V secondary star, giving a mass ratio of q = 0.83 +/- 0.05. On the basis of the component masses, and the spectral type and radius of the secondary star in V347 Pup, we find tentative evidence for an evolved companion. V347 Pup shows many of the characteristics of the SW Sex stars, exhibiting single-peaked emission lines, high-velocity S-wave components and phase-offsets in the radial velocity curve. We find spiral arms in the accretion disc of V347 Pup and measure the disc radius to be close to the maximum allowed in a pressureless disc.

The masses of the cataclysmic variables AC Cancri and V363 Aurigae

We present time-resolved spectroscopy and photometry of the double-lined eclipsing cataclysmic variables AC Cnc and V363 Aur (=Lanning 10). There is evidence of irradiation on the inner hemisphere of the secondary star in both systems, which we correct for using a model that reproduces the observations remarkably well. We find the radial velocity of the secondary star in AC Cnc to be K-R=176+/-3 km s(-1) and its rotational velocity to be v sin i=135+/-3 km s(-1). From these parameters we obtain masses of M-1=0.76+/-0.03 M-circle dot for the white-dwarf primary and M-2=0.77+/-0.05 M-circle dot for the K2+/-1 V secondary star, giving a mass ratio of q=1.02+/-0.04. We measure the radial and rotational velocities of the G7+/-2V secondary star in V363 Aur to be K-R=168+/-5 km s(-1) and v sin i=143+/-5 km s(-1), respectively. The component masses of V363 Aur are M-1=0.90+/-0.06M(circle dot) and M-2=1.06+/-0.11 M-circle dot giving a mass ratio of q=1.17+/-0.07. The mass ratios for AC Cnc and V363 Aur fall within the theoretical limits for dynamically and thermally stable mass transfer. Both systems are similar to the SW Sex stars, exhibiting single-peaked emission lines with transient absorption features, high-velocity S-wave components and phase-offsets in their radial-velocity curves. The Balmer lines in V363 Aur show a rapid increase in flux around phase 0 followed by a rapid decrease, which we attribute to the eclipse of an optically thick region at the centre of the disc. This model could also account for the behaviour of other SW Sex stars where the Balmer lines show only a shallow eclipse compared to the continuum.

Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase

Oestrogen produces diverse biological effects through binding to the oestrogen receptor (ER)(1). The ER is a steroid hormone nuclear receptor, which, when bound to oestrogen, modulates the transcriptional activity of target genes(2). Controversy exists, however, concerning whether ER has a role outside the nucleus(3), particularly in mediating the cardiovascular protective effects of oestrogen(4). Here we show that the ER isoform, ER alpha, binds in a ligand-dependent manner to the p85 alpha regulatory subunit of phosphatidylinositol-3-OH kinase (PI(3)K). Stimulation with oestrogen increases ER alpha-associated PI(3)K activity, leading to the activation of protein kinase B/Akt and endothelial nitric oxide synthase (eNOS). Recruitment and activation of PI(3)K by ligand-bound ERa are independent of gene transcription, do not involve phosphotyrosine adapter molecules or src-homology domains of p85 alpha, and extend to other steroid hormone receptors. Mice treated with oestrogen show increased eNOS activity and decreased vascular leukocyte accumulation after ischaemia and reperfusion injury. This vascular protective effect of oestrogen was abolished in the presence of PI(3)K or eNOS inhibitors. Our findings define a physiologically important non-nuclear oestrogen-signalling pathway involving the direct interaction of ERa with PI(3)K.