Protective and dysregulated T cell immunity in RSV infection

Respiratory syncytial virus (RSV) is the most important cause of infantile bronchiolitis and a major pathogen in elderly and immunosuppressed persons. Although RSV shows limited antigenic diversity, repeated infections occur throughout life. Vaccine development has been delayed by poor immunogenicity, production issues and the fear of causing enhanced disease. T cells assist in viral clearance, but immune regulation serves to limit these responses and to prevent the exaggerated inflammatory response to RSV infection seen in children with bronchiolitis. Severe RSV disease can therefore be regarded as a dysregulated response to an otherwise trivial infection. Further insights into the role of T cells (including Th17) are needed to enable the rational design of safe, effective vaccines and novel treatments

A slowly expanding disk and fast bipolar outflow from the S star π1 gruis

We study the molecular outflow of the nearby evolved S star π1 Gru. We imaged the outflow in CO J = 2-1 and dust continuum with the Submillimeter Array. The CO emission was detected over a very broad velocity width of ∼90 km s-1. Our high-resolution images show that the outflow at low velocities (≤15 km s-1) is elongated east-west and at high velocities (≥25 km s-1) is displaced north (at redshifted velocities) and south (blueshifted velocities) of center as defined by the dust continuum source. We model the spatial-kinematic structure of the low-velocity outflow as a flared disk with a central cavity of radius 200 AU and an expansion velocity of 11 km s-1, inclined by 55° to our line of sight. We attribute the high-velocity component to a bipolar outflow that emerges perpendicular to this disk with a velocity of up to ∼45 km s-1. This high-velocity outflow may play an important role in shaping the gas envelope previously ejected by the AGB star and thus produce a bipolar morphology when the object evolves into a proto-planetary nebula. © 2006. The American Astronomical Society. All rights reserved.published_or_final_versio

Rapid highly sensitive general protein quantification through on-chip chemiluminescence.

Protein detection and quantification is a routinely performed procedure in research laboratories, predominantly executed either by spectroscopy-based measurements, such as NanoDrop, or by colorimetric assays. The detection limits of such assays, however, are limited to μ M concentrations. To establish an approach that achieves general protein detection at an enhanced sensitivity and without necessitating the requirement for signal amplification steps or a multicomponent detection system, here, we established a chemiluminescence-based protein detection assay. Our assay specifically targeted primary amines in proteins, which permitted characterization of any protein sample and, moreover, its latent nature eliminated the requirement for washing steps providing a simple route to implementation. Additionally, the use of a chemiluminescence-based readout ensured that the assay could be operated in an excitation source-free manner, which did not only permit an enhanced sensitivity due to a reduced background signal but also allowed for the use of a very simple optical setup comprising only an objective and a detection element. Using this assay, we demonstrated quantitative protein detection over a concentration range of five orders of magnitude and down to a high sensitivity of 10 pg mL - 1 , corresponding to pM concentrations. The capability of the platform presented here to achieve a high detection sensitivity without the requirement for a multistep operation or a multicomponent optical system sets the basis for a simple yet universal and sensitive protein detection strategy.Engineering and Physical Sciences Research Council Schmidt Science Fellows program in partnership with the Rhodes Trust European Research Council Newman Foundatio

Radiological findings in patients undergoing revision endoscopic sinus surgery: a retrospective case series study

<p>Abstract</p> <p>Background</p> <p>Functional endoscopic sinus surgery (FESS) is now a well-established strategy for the treatment of chronic rhinosinusitis which has not responded to medical treatment. There is a wide variation in the practice of FESS by various surgeons within the UK and in other countries.</p> <p>Objectives</p> <p>To identify anatomic factors that may predispose to persistent or recurrent disease in patients undergoing revision FESS.</p> <p>Methods</p> <p>Retrospective review of axial and coronal CT scans of patients undergoing revision FESS between January 2005 and November 2008 in a tertiary referral centre in South West of England.</p> <p>Results</p> <p>The CT scans of 63 patients undergoing revision FESS were reviewed. Among the patients studied, 15.9% had significant deviation of the nasal septum. Lateralised middle turbinates were present in 11.1% of the studied sides, and residual uncinate processes were identified in 57.1% of the studied sides. There were residual cells in the frontal recess in 96% of the studied sides. There were persistent other anterior and posterior ethmoidal cells in 92.1% and 96% of the studied sides respectively.</p> <p>Conclusions</p> <p>Analysis of CT scans of patients undergoing revision FESS shows persistent structures and non-dissected cells that may be responsible for persistence or recurrence of rhinosinusitis symptoms. Trials comparing the outcome of conservative FESS techniques with more radical sinus dissections are required.</p

Impaired antibody-mediated protection and defective IgA B cell memory in experimental infection of adults with respiratory syncytial virus

Rationale: Despite relative antigenic stability, respiratory syncytial virus (RSV) re-infects throughout life. After >40 years of research, no effective human vaccine exists and correlates of protection remain poorly defined. Most current vaccine candidates seek to induce high levels of RSV-specific serum neutralizing antibodies, which are associated with reduced RSV-related hospitalization rates in observational studies but may not actually prevent infection. Objectives: Characterize correlates of protection from infection and the generation of RSV-specific humoral memory to promote effective vaccine development. Methods: We inoculated 61 healthy adults with live RSV and studied protection from infection by serum and mucosal antibody. We analyzed RSV-specific peripheral blood plasmablast and memory B cell frequencies and antibody longevity. Measurements and Main Results: Despite moderately high levels of pre-existing serum antibody, 34 (56%) became infected, of whom 23 (68%) developed symptomatic colds. Prior RSV-specific nasal IgA correlated significantly more strongly with protection from PCR-confirmed infection than serum neutralizing antibody. Increases in virus-specific antibody titers were variable and transient in infected subjects, but correlated with plasmablasts that peaked around day 10. During convalescence, only IgG (and no IgA) RSV-specific memory B cells were detectable in peripheral blood. This contrasted with natural influenza infection, where virus-specific IgA memory B cells were readily recovered. Conclusions: This observed specific defect in IgA memory may partly explain RSV's ability to cause recurrent symptomatic infections. If so, vaccines able to induce durable RSV-specific IgA responses may be more protective than those generating systemic antibody alone

Impaired antibody-mediated protection and defective IgA B cell memory in experimental infection of adults with respiratory syncytial virus

Rationale: Despite relative antigenic stability, respiratory syncytial virus (RSV) re-infects throughout life. After >40 years of research, no effective human vaccine exists and correlates of protection remain poorly defined. Most current vaccine candidates seek to induce high levels of RSV-specific serum neutralizing antibodies, which are associated with reduced RSV-related hospitalization rates in observational studies but may not actually prevent infection. Objectives: Characterize correlates of protection from infection and the generation of RSV-specific humoral memory to promote effective vaccine development. Methods: We inoculated 61 healthy adults with live RSV and studied protection from infection by serum and mucosal antibody. We analyzed RSV-specific peripheral blood plasmablast and memory B cell frequencies and antibody longevity. Measurements and Main Results: Despite moderately high levels of pre-existing serum antibody, 34 (56%) became infected, of whom 23 (68%) developed symptomatic colds. Prior RSV-specific nasal IgA correlated significantly more strongly with protection from PCR-confirmed infection than serum neutralizing antibody. Increases in virus-specific antibody titers were variable and transient in infected subjects, but correlated with plasmablasts that peaked around day 10. During convalescence, only IgG (and no IgA) RSV-specific memory B cells were detectable in peripheral blood. This contrasted with natural influenza infection, where virus-specific IgA memory B cells were readily recovered. Conclusions: This observed specific defect in IgA memory may partly explain RSV's ability to cause recurrent symptomatic infections. If so, vaccines able to induce durable RSV-specific IgA responses may be more protective than those generating systemic antibody alone

Automated simultaneous analysis phylogenetics (ASAP) : an enabling tool for phlyogenomics

© 2008 Sarkar et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License 2.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in BMC Bioinformatics 9 (2008): 103, doi:10.1186/1471-2105-9-103.The availability of sequences from whole genomes to reconstruct the tree of life has the potential to enable the development of phylogenomic hypotheses in ways that have not been before possible. A significant bottleneck in the analysis of genomic-scale views of the tree of life is the time required for manual curation of genomic data into multi-gene phylogenetic matrices. To keep pace with the exponentially growing volume of molecular data in the genomic era, we have developed an automated technique, ASAP (Automated Simultaneous Analysis Phylogenetics), to assemble these multigene/multi species matrices and to evaluate the significance of individual genes within the context of a given phylogenetic hypothesis. Applications of ASAP may enable scientists to re-evaluate species relationships and to develop new phylogenomic hypotheses based on genome-scale data.This work is funded in part by NSF DBI-0421604 to GC and RD. INS is supported in part by the Ellison Medical Foundation

High School Students' Proficiency and Confidence Levels in Displaying Their Understanding of Basic Electrolysis Concepts

This study was conducted with 330 Form 4 (grade 10) students (aged 15 – 16 years) who were involved in a course of instruction on electrolysis concepts. The main purposes of this study were (1) to assess high school chemistry students’ understanding of 19 major principles of electrolysis using a recently developed 2-tier multiple-choice diagnostic instrument, the Electrolysis Diagnostic Instrument (EDI), and (2) to assess students’ confidence levels in displaying their knowledge and understanding of these electrolysis concepts. Analysis of students’ responses to the EDI showed that they displayed very limited understanding of the electrolytic processes involving molten compounds and aqueous solutions of compounds, with a mean score of 6.82 (out of a possible maximum of 17). Students were found to possess content knowledge about several electrolysis processes but did not provide suitable explanations for the changes that had occurred, with less than 45 % of students displaying scientifically acceptable understandings about electrolysis. In addition, students displayed limited confidence about making the correct selections for the items; yet, in 16 of the 17 items, the percentage of students who were confident that they had selected the correct answer to an item was higher than the actual percentage of students who correctly answered the corresponding item. The findings suggest several implications for classroom instruction on the electrolysis topic that need to be addressed in order to facilitate better understanding by students of electrolysis concepts

The availability of novelty sweets within the high school fringe

Background Reducing sugar consumption is a primary focus of current global public health policy. Achieving 5% of total energy from free sugars will be difficult acknowledging the concentration of free sugars in sugar sweetened beverages, confectionery and as hidden sugars in many savoury items. The expansion of the novelty sweet market in the UK has significant implications for children and young adults as they contribute to dental caries, dental erosion and obesity. Objective To identify the most available types of novelty sweets within the high school fringe in Cardiff, UK and to assess their price range and where and how they were displayed in shops. Subjects and methods Shops within a ten minute walking distance around five purposively selected high schools in the Cardiff aea representing different levels of deprivation were visited. Shops in Cardiff city centre and three supermarkets were also visited to identify the most commonly available novelty sweets. Results The ten most popular novelty sweets identified in these scoping visits were (in descending order): Brain Licker, Push Pop, Juicy Drop, Lickedy Lips, Big Baby Pop, Vimto candy spray, Toxic Waste, Tango candy spray, Brain Blasterz Bitz and Mega Mouth candy spray. Novelty sweets were located on low shelves which were accessible to all age-groups in 73% (14 out of 19) of the shops. Novelty sweets were displayed in the checkout area in 37% (seven out of 19) shops. The price of the top ten novelty sweets ranged from 39p to £1. Conclusion A wide range of acidic and sugary novelty sweets were easily accessible and priced within pocket money range. Those personnel involved in delivering dental and wider health education or health promotion need to be aware of recent developments in children's confectionery. The potential effects of these novelty sweets on both general and dental health require further investigation