A Cysteine Zipper Stabilizes a Pre-Fusion F Glycoprotein Vaccine for Respiratory Syncytial Virus.

Recombinant subunit vaccines should contain minimal non-pathogen motifs to reduce potential off-target reactivity. We recently developed a vaccine antigen against respiratory syncytial virus (RSV), which comprised the fusion (F) glycoprotein stabilized in its pre-fusion trimeric conformation by "DS-Cav1" mutations and by an appended C-terminal trimerization motif or "foldon" from T4-bacteriophage fibritin. Here we investigate the creation of a cysteine zipper to allow for the removal of the phage foldon, while maintaining the immunogenicity of the parent DS-Cav1+foldon antigen.

Novel antigens for RSV vaccines.

Respiratory syncytial virus (RSV) remains a leading global cause of infant mortality and adult morbidity. Infection, which recurs throughout life, elicits only short-lived immunity. The development of a safe and efficacious vaccine has, thus far, been elusive.

Neutralizing epitopes on the respiratory syncytial virus fusion glycoprotein.

Respiratory syncytial virus (RSV) is a leading cause of pneumonia and bronchiolitis, but despite decades of research a safe and effective vaccine has remained elusive. The viral fusion glycoprotein (RSV F) plays an obligatory role in the entry process and is the major target of neutralizing antibodies, making it an attractive target for vaccine development. This review will summarize the recently determined structures of RSV F in the prefusion and postfusion conformations and describe the location and properties of neutralizing epitopes on RSV F, including the newly identified prefusion-specific epitopes.

Effectiveness of school-based smoking prevention curricula: systematic review and meta-analysis.

Objective: To assess effectiveness of school-based smoking prevention curricula keeping children never-smokers.

Design: Systematic review, meta-analysis.

Data: MEDLINE (1966+), EMBASE (1974+), Cinahl, PsycINFO (1967+), ERIC (1982+), Cochrane CENTRAL, Health Star, Dissertation Abstracts, conference proceedings.

Structural definition of an antibody-dependent cellular cytotoxicity response implicated in reduced risk for HIV-1 infection.

Unlabelled: The RV144 vaccine trial implicated epitopes in the C1 region of gp120 (A32-like epitopes) as targets of potentially protective antibody-dependent cellular cytotoxicity (ADCC) responses. A32-like epitopes are highly immunogenic, as infected or vaccinated individuals frequently produce antibodies specific for these determinants. Antibody titers, as measured by enzyme-linked immunosorbent assay (ELISA) against these epitopes, however, do not consistently correlate with protection.

Infection with MERS-CoV causes lethal pneumonia in the common marmoset.

The availability of a robust disease model is essential for the development of countermeasures for Middle East respiratory syndrome coronavirus (MERS-CoV). While a rhesus macaque model of MERS-CoV has been established, the lack of uniform, severe disease in this model complicates the analysis of countermeasure studies. Modeling of the interaction between the MERS-CoV spike glycoprotein and its receptor dipeptidyl peptidase 4 predicted comparable interaction energies in common marmosets and humans.

Host species restriction of Middle East respiratory syndrome coronavirus through its receptor, dipeptidyl peptidase 4.

Unlabelled: Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike protein and DPP4 was determined by crystallography. Animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS-CoV.

Structure and function of respiratory syncytial virus surface glycoproteins.

The two major glycoproteins on the surface of the respiratory syncytial virus (RSV) virion, the attachment glycoprotein (G) and the fusion glycoprotein (F), control the initial phases of infection. G targets the ciliated cells of the airways, and F causes the virion membrane to fuse with the target cell membrane. The F protein is the major target for antiviral drug development, and both G and F glycoproteins are the antigens targeted by neutralizing antibodies induced by infection.

Perceptions of postnatal care: factors associated with primiparous mothers perceptions of postnatal communication and care.

Background: The aim of this study was to determine whether personality and/or psychological functioning affect mothers' perceptions of postnatal communication and their level of satisfaction with their postnatal care. Mothers' perceptions of the communication with health professionals prenatally and during birth may be affected by their personality traits and psychological functioning and are linked to the level of satisfaction they have in their healthcare. Little is known about factors that are associated with perceptions of communication within postnatal care and the impact this may have on satisfaction with care.

Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus.

Respiratory syncytial virus (RSV) is the leading cause of hospitalization for children under 5 years of age. We sought to engineer a viral antigen that provides greater protection than currently available vaccines and focused on antigenic site Ø, a metastable site specific to the prefusion state of the RSV fusion (F) glycoprotein, as this site is targeted by extremely potent RSV-neutralizing antibodies. Structure-based design yielded stabilized versions of RSV F that maintained antigenic site Ø when exposed to extremes of pH, osmolality, and temperature.

Does periosteal scraping of the third metacarpal bone reduce the incidence of 'bucked shins' in young Thoroughbred racehorses?

Reasons For Performing Study: The occurrence of bucked shins in young Thoroughbred racehorses in North America is high. Although an altered training regime has demonstrated a significant decrease in this condition, trainers can be opposed to altering something as fundamental as their training routine. Periosteal scraping of the third metacarpal bone (McIII) is a putative prophylactic technique used to prevent bucked shins; therefore, a study to investigate the validity of the procedure is warranted.

Repair of umbilical and epigastric hernias.

Umbilical and epigastric hernias are primary midline defects that are present in up to 50% of the population. In the United States, only about 1% of the population carries this specific diagnosis, and only about 11% of these are repaired. Repair is aimed at symptoms relief or prevention, and the patient's goals and expectations should be explicitly identified and aligned with the health care team.

The effect of insertional suspensory branch desmitis on racing performance in juvenile Thoroughbred racehorses.

Reasons For Performing The Study: Limited information exists regarding the prognosis for juvenile racehorses sustaining injury to the suspensory ligament branch insertion (JISBI).

Objectives: To investigate the effect of JISBI on racing performance; and to assess whether the severity of JISBI is prognostically important.

Study Design: Retrospective cohort study.

Do radiographic signs of sesamoiditis in yearling Thoroughbreds predispose the development of suspensory ligament branch injury?

Reasons For Performing Study: Sesamoiditis is believed to be associated with injury to the suspensory branch attachment and is a common radiographic finding in yearling Thoroughbreds. No study has investigated relationships between yearling sesamoiditis and subsequent development of suspensory ligament branch injury (SLBI) in early racehorse training.

Objectives: To establish the prevalence of SLBI within a population of juvenile training racehorses and retrospectively investigate relationships between clinical signs of SLBI and sesamoiditis to determine if sesamoiditis is a risk factor for clinical suspensory branch injury.

Synthetic glycopeptides reveal the glycan specificity of HIV-neutralizing antibodies.

A new class of glycan-reactive HIV-neutralizing antibodies, including PG9 and PG16, has been recently discovered that seem to recognize previously uncharacterized glycopeptide epitopes on HIV-1 gp120. However, further characterization and reconstitution of the precise neutralizing epitopes are complicated by the heterogeneity of glycosylation. We report here the design, synthesis and antigenic evaluation of new cyclic V1V2 glycopeptides carrying defined N-linked glycans at the conserved glycosylation sites (Asn160 and Asn156 or Asn173) derived from gp120 of two HIV-1 isolates.

Autoinflation for hearing loss associated with otitis media with effusion.

Background: This is an update of a Cochrane review first published in The Cochrane Library in Issue 4, 2006.Otitis media with effusion (OME) or 'glue ear' is an accumulation of fluid in the middle ear, in the absence of acute inflammation or infection. It is the commonest cause of acquired hearing loss in childhood and the usual reason for insertion of 'grommets'.

Structural basis for diverse N-glycan recognition by HIV-1-neutralizing V1-V2-directed antibody PG16.

HIV-1 uses a diverse N-linked-glycan shield to evade recognition by antibody. Select human antibodies, such as the clonally related PG9 and PG16, recognize glycopeptide epitopes in the HIV-1 V1-V2 region and penetrate this shield, but their ability to accommodate diverse glycans is unclear. Here we report the structure of antibody PG16 bound to a scaffolded V1-V2, showing an epitope comprising both high mannose-type and complex-type N-linked glycans.

School-based programmes for preventing smoking.

Background: Helping young people to avoid starting smoking is a widely endorsed public health goal, and schools provide a route to communicate with nearly all young people. School-based interventions have been delivered for close to 40 years.

Objectives: The primary aim of this review was to determine whether school smoking interventions prevent youth from starting smoking.

Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody.

The prefusion state of respiratory syncytial virus (RSV) fusion (F) glycoprotein is the target of most RSV-neutralizing activity in human sera, but its metastability has hindered characterization. To overcome this obstacle, we identified prefusion-specific antibodies that were substantially more potent than the prophylactic antibody palivizumab. The cocrystal structure for one of these antibodies, D25, in complex with the F glycoprotein revealed D25 to lock F in its prefusion state by binding to a quaternary epitope at the trimer apex.

N332-Directed broadly neutralizing antibodies use diverse modes of HIV-1 recognition: inferences from heavy-light chain complementation of function.

Dozens of broadly neutralizing HIV-1 antibodies have been isolated in the last few years from the sera of HIV-1-infected individuals. Only a limited number of regions on the HIV-1 spike, however, are recognized by these antibodies. One of these regions (N332) is characterized by an N-linked glycan at residue 332 on HIV-1 gp120 and is recognized by antibody 2G12 and by the recently reported antibodies PGT121-137, the latter isolated from three donors.

Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2.

The RV144 HIV-1 trial of the canary pox vector (ALVAC-HIV) plus the gp120 AIDSVAX B/E vaccine demonstrated an estimated efficacy of 31%, which correlated directly with antibodies to HIV-1 envelope variable regions 1 and 2 (V1-V2). Genetic analysis of trial viruses revealed increased vaccine efficacy against viruses matching the vaccine strain at V2 residue 169. Here, we isolated four V2 monoclonal antibodies from RV144 vaccinees that recognize residue 169, neutralize laboratory-adapted HIV-1, and mediate killing of field-isolate HIV-1-infected CD4(+) T cells.

Vulnerability of larval and juvenile white sturgeon to barotrauma: can they handle the pressure?

Techniques were developed to determine which life stages of fish are vulnerable to barotrauma from expansion of internal gases during decompression. Eggs, larvae, and juvenile hatchery-reared white sturgeon (Acipenser transmontanus; up to 91 days post hatch; d.p.