Giving New Zealand: Philanthropic Funding 2006

This report provides measurement of New Zealanders' philanthropic funding for the 2005/2006 year and what these funds supported

The mucosal firewalls against commensal intestinal microbes

Mammals coexist with an extremely dense microbiota in the lower intestine. Despite the constant challenge of small numbers of microbes penetrating the intestinal surface epithelium, it is very unusual for these organisms to cause disease. In this review article, we present the different mucosal firewalls that contain and allow mutualism with the intestinal microbiot

Memetic: from meeting memory to virtual ethnography & distributed video analysis

The JISC-funded Memetic2 project was designed as knowledge management and project memory support for teams meeting via the Access Grid environment (Buckingham Shum et al, 2006). This paper describes how these capabilities also enable it to serve as a novel distributed video analysis tool to support interaction analysis. Memetic technologies can be used to record, annotate and discuss sessions recorded within a flexible, visual hypermedia environment called Compendium. We propose that beyond the use originally conceived, the Memetic toolset could find wide ranging applications within social science for virtual ethnography and data analysis

User-centered development of a Virtual Research Environment to support collaborative research events

This paper discusses the user-centred development process within the Collaborative Research Events on the Web (CREW) project, funded under the JISC Virtual Research Environments (VRE) programme. After presenting the project, its aims and the functionality of the CREW VRE, we focus on the user engagement approach, grounded in the method of co-realisation. We describe the different research settings and requirements of our three embedded user groups and the respective activities conducted so far. Finally we elaborate on the main challenges of our user engagement approach and end with the project’s next steps

Interferon-stimulated gene (ISG)-expression screening reveals the specific antibunyaviral activity of ISG20

Bunyaviruses pose a significant threat to human health, prosperity and food security. In response to viral infections, interferons (IFNs) upregulate the expression of hundreds of interferon stimulated genes (ISGs) whose cumulative action can potently inhibit the replication of bunyaviruses. We used a flow cytometry-based method to screen the ability of ∼500 unique ISGs from humans and rhesus macaques to inhibit the replication of Bunyamwera orthobunyavirus (BUNV), the prototype of both the Peribunyaviridae family and Bunyavirales order. Candidates possessing antibunyaviral activity were further examined using a panel of divergent bunyaviruses. Interestingly, one candidate, ISG20, exhibited potent antibunyaviral activity against most viruses examined from the Peribunyaviridae, Hantaviridae and Nairoviridae families, whereas phleboviruses (Phenuiviridae) largely escaped inhibition. Similar to other viruses known to be targeted by ISG20, the antibunyaviral activity of ISG20 is dependent upon its functional ribonuclease activity. Through use of an infectious VLP assay (based on the BUNV minigenome system), we confirmed that gene expression from all 3 viral segments is strongly inhibited by ISG20. Using in vitro evolution, we generated a substantially ISG20-resistant BUNV and mapped the determinants of ISG20 sensitivity/resistance. Taken together, we report that ISG20 is a broad and potent antibunyaviral factor yet some bunyaviruses are remarkably ISG20 resistant. Thus, ISG20 sensitivity/resistance could influence the pathogenesis of bunyaviruses, many of which are emerging viruses of clinical or veterinary significance

Haemophilus influenzae Type b Vaccine Failure in Children Is Associated with Inadequate Production of High-Quality Antibody

Background. Despite the excellent immunogenicity of Haemophilus influenzae type b (Hib) conjugate vaccines, breakthrough cases of Hib disease still affect a small proportion of vaccinated children in the United Kingdom. We performed a retrospective study to compare the avidity of antibody directed against the Hib polysaccharide capsule (PRP) in children who experienced Hib vaccine failure in the United Kingdom among 3 historical cohorts and with age-matched healthy control subjects. Methods. Serum samples from vaccinated children with invasive Hib disease were collected beginning in 1992 as part of enhanced surveillance for Hib disease following vaccine introduction. A total of 251 children who experienced Hib vaccine failure were identified from 3 historical cohorts (1992-1995, 1996-1999, and 2000-2003). The anti-PRP antibody concentration and avidity from healthy age-matched control subjects was obtained for the 3 contemporary time points (1995, 1999, and 2002). Serum anti-PRP antibody concentration was measured in each of the samples using a standard Hib ELISA, and antibody avidity was determined using thiocyanate elution. Results. Within the first 60 days after disease onset, there was no change in the anti-PRP antibody avidity, and there was no statistically significant difference in the geometric mean Hib antibody avidity over the 3 study periods. However, the children who experienced Hib vaccine failure had significantly lower Hib antibody avidity than did healthy control subjects, despite a marked antibody response following infection. Conclusions. Children who experience Hib disease despite vaccination appear to have a defect in immunological priming, leading to a qualitative difference in Hib-specific memory B cells. Low anti-PRP antibody avidity decreases the functional activity of anti-PRP antibody in the sera of these children experiencing vaccine failure, leading to disease susceptibilit

Large sugar pine (Pinus lambertiana) vigor and mortality in a fire-excluded forest of the central Sierra Nevada

In recent decades rapid environmental change has led to significant shifts in forest dynamics across the western United States. In particular, fire exclusion has led to denser forests with higher competitive stress, and climate change has increased temperatures, and affected water availability by altering snowmelt and evapotranspiration. As a result, tree vigor for many species has declined and contributed to increased rates of tree mortality, especially for large and old trees. Large trees provide important ecological services, but are rare on the landscape due to past logging activities. Therefore, forest managers have focused restoration efforts to improve old-growth forests conditions. However, the impact of environmental stress on tree vigor and mortality is a complicated process and more information about the relative importance of climate and competition is needed. This study investigated tree vigor and mortality for large sugar pine (Pinus lambertiana) in response to climate and competition at the Stanislaus-Tuolumne Experimental Forest in the Sierra Nevada. This mixed-conifer forest has experienced a long period of fire exclusion and increased warming that has likely contributed to greater vulnerability of large sugar pine to pathogen (e.g. white pine blister rust) and bark beetle attacks. Tree vigor was examined by analyzing annual measurements of growth (i.e. basal area increment, BAI) and resin duct defenses. Chapter 1 examined the response of large sugar pine growth and defense to climate (i.e. temperature, precipitation, climatic water deficit), and retrospective competition using generalized linear mixed models. Chapter 2 modeled the relative importance of growth, defense, and competition on the probability of large sugar pine mortality using logistic regression. Reduced BAI in large sugar pine was more strongly associated with lower January temperatures, less precipitation from the previous October through December, higher interspecific competition, and higher intraspecific competition (R2 = 0.81, RMSE = 9.96). Resin duct size was most associated with water deficit, precipitation from the previous October- current April, and total competition (R2 = 0.66, RMSE = 0.022). Resin duct total area was associated with water deficit, precipitation from the previous October- current April, total competition, and the interaction of total competition with June temperature (R2 = 0.54, RMSE = 0.2108). Measures of competition had a stronger relationship with large sugar pine growth and defense when compared to measures of climate. The best model of large sugar pine mortality included growth, defense, and competition variables. Declining growth (i.e. the slope of BAI) and lower growth variability during the 10 years before mortality had the greatest association with mortality (area under ROC = 0.93). Internal validation of the top mortality model correctly classified 87.9% of dead sugar pine and 84.8% of live sugar pine. Results from this study highlight some of the trade-offs between growth and defense in response to climate and competition, and the importance of declining growth and defense leading to a higher probability of mortality.Thesis (M.S.)--Humboldt State University, Natural Resources, 201

Development of a Multiple-Locus Variable number of tandem repeat Analysis (MLVA) for Leptospira interrogans and its application to Leptospira interrogans serovar Australis isolates from Far North Queensland, Australia

BACKGROUND: Leptospirosis is a zoonotic disease caused by the genus, Leptospira. Leptospira interrogans is the most common genomospecies implicated in the disease. Epidemiological investigations are needed to distinguish outbreak situations or to trace reservoirs of the organisms. Current methodologies used for typing Leptospira have significant drawbacks. The development of an easy to perform yet high resolution method is needed for this organism. METHODS: In this study we have searched the available genomic sequence of L. interrogans serovar Copenhageni strain Fiocruz L1-130 for the presence of tandem repeats [1]. These repeats were evaluated against reference strains for diversity. Six loci were selected to create a Multiple Locus Variable Number of Tandem Repeats (VNTR) Analysis (MLVA) to explore the genetic diversity within L. interrogans serovar Australis clinical isolates from Far North Queensland. RESULTS: The 39 reference strains used for the development of the method displayed 39 distinct patterns. Diversity Indexes for the loci varied between 0.80 and 0.93 and the number of repeat units at each locus varied between less than one to 52 repeats. When the MLVA was applied to serovar Australis isolates three large clusters were distinguishable, each comprising various hosts including Rattus species, human and canines. CONCLUSION: The MLVA described in this report, was easy to perform, analyse and was reproducible. The loci selected had high diversity allowing discrimination between serovars and also between strains within a serovar. This method provides a starting point on which improvements to the method and comparisons to other techniques can be made

Identification of pathogenic Leptospira species by conventional or real-time PCR and sequencing of the DNA gyrase subunit B encoding gene

BACKGROUND: Leptospira is the causative genus of the disease, leptospirosis. Species identification of pathogenic Leptospira in the past was generally performed by either DNA-DNA hybridisation or 16s rRNA gene sequencing. Both methods have inherent disadvantages such as the need for radio-labelled isotopes or significant homology between species. A conventional and real-time PCR amplification and sequencing method was developed for an alternate gene target: DNA gyrase subunit B (gyrB). Phylogenetic comparisons were undertaken between pathogenic Leptospira 16srRNA and gyrB genes using clustering and minimum evolution analysis. In addition 50 unidentified Leptospira isolates were characterised by gyrB sequencing and compared with conventional 16s rRNA sequencing. RESULTS: A conventional and real-time PCR methodology was developed and optimised for the amplification of the gyrB from pathogenic Leptospira species. Non pathogenic and opportunistic Leptospira species such as L. fainei and L. broomi were not amplified. The gyrB gene shows greater nucleotide divergence (3.5% to 16.1%) than the 16s rRNA gene (0.1% to 1.4%). Minimum evolution analysis reveals that the gyrB has a different evolution topology for L. kirschneri and L. interrogans. When the two genes were compared for the identification of the 50 unknown isolates there was 100% agreement in the results. CONCLUSION: This research has successfully developed a methodology for the identification of pathogenic Leptospira using an alternate gene to 16s rRNA. The gyrB encoding gene shows higher nucleotide/evolutionary divergence allowing for superior identification and also the potential for the development of DNA probe based identification