Recrudescent Infection Supports Hendra Virus Persistence in Australian Flying-Fox Populations

Zoonoses from wildlife threaten global public health. Hendra virus is one of several zoonotic viral diseases that have recently emerged from Pteropus species fruit-bats (flying-foxes). Most hypotheses regarding persistence of Hendra virus within flying-fox populations emphasize horizontal transmission within local populations (colonies) via urine and other secretions, and transmission among colonies via migration. As an alternative hypothesis, we explore the role of recrudescence in persistence of Hendra virus in flying-fox populations via computer simulation using a model that integrates published information on the ecology of flying-foxes, and the ecology and epidemiology of Hendra virus. Simulated infection patterns agree with infection patterns observed in the field and suggest that Hendra virus could be maintained in an isolated flying-fox population indefinitely via periodic recrudescence in a manner indistinguishable from maintenance via periodic immigration of infected individuals. Further, post-recrudescence pulses of infectious flying-foxes provide a plausible basis for the observed seasonal clustering of equine cases. Correct understanding of the infection dynamics of Hendra virus in flying-foxes is fundamental to effectively managing risk of infection in horses and humans. Given the lack of clear empirical evidence on how the virus is maintained within populations, the role of recrudescence merits increased attention.

Seed bank persistence and germination of chinee apple (Ziziphus mauritiana Lam.)

Chinee apple (Ziziphus mauritiana Lam.) is a thorny tree that is invading tropical woodlands of northern Australia. The present study reports three experiments related to the seed dynamics of chinee apple. Experiment 1 and 2 investigated persistence of seed lots under different soil types (clay and river loam), levels of pasture cover (present or absent) and burial depths (0, 2.5, 10 and 20 cm). Experiment 3 determined the germination response of chinee apple seeds to a range of alternating day/night temperatures (11/6°C up to 52/40°C). In the longevity experiments (Expts 1 and 2), burial depth, soil type and burial duration significantly affected viability. Burial depth had the greatest influence, with surface located seeds generally persisting for longer than those buried below ground. Even so, no viable seeds remained after 18 and 24 months in the first and second experiment, respectively. In Expt 3 seeds of chinee apple germinated under a wide range of alternating day/night temperatures ranging from 16/12°C to 47 /36°C. Optimal germination (77%) occurred at 33/27°C and no seeds germinated at either of the lowest (11/6°C) or highest (52/40°C) temperature regimes tested. These findings indicated that chinee apple has the potential to expand its current distribution to cooler areas of Australia. Control practices need to be undertaken for at least two years to exhaust the seed bank.

Persistence is fertile: Pushing methodological potentialities in education research

As more is known about contemporary cultural shifts and the effect this has on the young, research must consider how children operate as global citizens. Children are innocent and vulnerable, but also actively participate in the world; research into early childhood must therefore refine ideas and conceptions and develop research methodologies that see children as superdiverse young citizens. Intergenerational collaborative drawing, which involves adult researchers and children drawing together, is a method that supports superdimensions. A group of researchers tested the method to consider the politics of research, particularly when researcher neutrality and the conventions around gathering ‘unsullied’ data are challenged.

Human parvovirus B19: tissue persistence and prevalence of prototypic and new variants

Human parvovirus B19 is a minute ssDNA virus causing a wide variety of diseases, including erythema infectiosum, arthropathy, anemias, and fetal death. After primary infection, genomic DNA of B19 has been shown to persist in solid tissues of not only symptomatic but also of constitutionally healthy, immunocompetent individuals. In this thesis, the viral DNA was shown to persist as an apparently intact molecule of full length, and without persistence-specific mutations. Thus, although the mere presence of B19 DNA in tissue can not be used as a diagnostic criterion, a possible role in the pathogenesis of diseases e.g. through mRNA or protein production can not be excluded. The molecular mechanism, the host-cell type and the possible clinical significance of B19 DNA tissue persistence are yet to be elucidated. In the beginning of this work, the B19 genomic sequence was considered highly conserved. However, new variants were found: V9 was detected in 1998 in France, in serum of a child with aplastic crisis. This variant differed from the prototypic B19 sequences by ~10 %. In 2002 we found, persisting in skin of constitutionally healthy humans, DNA of another novel B19 variant, LaLi. Genetically this variant differed from both the prototypic sequences and the variant V9 also by ~10%. Simultaneously, B19 isolates with DNA sequences similar to LaLi were introduced by two other groups, in the USA and France. Based on phylogeny, a classification scheme based on three genotypes (B19 types 1-3) was proposed. Although the B19 virus is mainly transmitted via the respiratory route, blood and plasma-derived products contaminated with high levels of B19 DNA have also been shown to be infectious. The European Pharmacopoeia stipulates that, in Europe, from the beginning of 2004, plasma pools for manufacture must contain less than 104 IU/ml of B19 DNA. Quantitative PCR screening is therefore a prerequisite for restriction of the B19 DNA load and obtaining of safe plasma products. Due to the DNA sequence variation among the three B19 genotypes, however, B19 PCR methods might fail to detect the new variants. We therefore examined the suitability of the two commercially available quantitative B19 PCR tests, LightCycler-Parvovirus B19 quantification kit (Roche Diagnostics) and RealArt Parvo B19 LC PCR (Artus), for detection, quantification and differentiation of the three B19 types known, including B19 types 2 and 3. The former method was highly sensitive for detection of the B19 prototype but was not suitable for detection of types 2 and 3. The latter method detected and differentiated all three B19 virus types. However, one of the two type-3 strains was detected at a lower sensitivity. Then, we assessed the prevalence of the three B19 virus types among Finnish blood donors, by screening pooled plasma samples derived from >140 000 blood-donor units: none of the pools contained detectable levels of B19 virus types 2 or 3. According to the results of other groups, B19 type 2 was absent also among Danish blood-donors, and extremely rare among symptomatic European patients. B19 type 3 has been encountered endemically in Ghana and (apparently) in Brazil, and sporadical cases have been detected in France and the UK. We next examined the biological characteristics of these virus types. The p6 promoter regions of virus types 1-3 were cloned in front of a reporter gene, the constructs were transfected into different cell lines, and the promoter activities were measured. As a result, we found that the activities of the three p6 promoters, although differing in sequence by >20%, were of equal strength, and most active in B19-permissive cells. Furthermore, the infectivity of the three B19 types was examined in two B19-permissive cell lines. RT-PCR revealed synthesis of spliced B19 mRNAs, and immunofluorescence verified the production of NS1 and VP proteins in the infected cells. These experiments suggested similar host-cell tropism and showed that the three virus types are strains of the same species, i.e. human parvovirus B19. Last but not least, the sera from subjects infected in the past either with B19 type 1 or type 2 (as evidenced by tissue persistence of the respective DNAs), revealed in VP1/2- and VP2-EIAs a 100 % cross-reactivity between virus types 1 and 2. These results, together with similar studies by others, indicate that the three B19 genotypes constitute a single serotype.

Activation and persistence of implicit causality information in spoken language comprehension

A visual world eye-tracking study investigated the activation and persistence of implicit causality information in spoken language comprehension. We showed that people infer the implicit causality of verbs as soon as they encounter such verbs in discourse, as is predicted by proponents of the immediate focusing account (Greene & McKoon, 1995; Koornneef & Van Berkum, 2006; Van Berkum, Koornneef, Otten, & Nieuwland, 2007). Interestingly, we observed activation of implicit causality information even before people encountered the causal conjunction. However, while implicit causality information was persistent as the discourse unfolded, it did not have a privileged role as a focusing cue immediately at the ambiguous pronoun when people were resolving its antecedent. Instead, our study indicated that implicit causality does not affect all referents to the same extent, rather it interacts with other cues in the discourse, especially when one of the referents is already prominently in focus.

Performance Persistence of International Stock Funds

People saving in mutual funds often look at historical performance before they decide which funds to invest in. The implicit assumption made is that superior performance is likely to be repeated in the future. The findings presented in this study, which investigates funds sold on the Swedish market, support such an approach provided that the time horizons are limited to one year. International stock funds that have performed strongly one year are likely to outperform their peers also the following years. But if the historical and future time horizons are extended to two or three years, the positive relationship between past and future performance vanishes in most cases. Persistence tests focusing on the aggregated performance of fund companies were also carried out. These tests produced results rather similar to those on the individual fund level.

Mother-Infant Antibodies to Pneumococcal Polysaccharides and Proteins : Transfer and Persistence of Maternal Antibodies and Development of Vaccine-Induced and Naturally Acquired Antibodies in Infants

Symptomless nasopharyngeal carriage of Streptococcus pneumoniae (pneumococcus) is very common in young children. Occasionally the carriage proceeds into mild mucosal diseases, such as sinusitis or acute otitis media, or into serious life-threatening diseases, such as pneumonia, sepsis or meningitis. Each year, up to one million children less than five years of age worldwide die of invasive pneumococcal diseases (IPD). Especially in the low-income countries IPD is a leading health problem in infants; 75% of all IPD cases occur before one year of age. This stresses the need of increased protection against pneumococcus in infancy. Anti-pneumococcal antibodies form an important component in the defence against pneumococcal infection. Maternal immunisation and early infant immunisation are two possible ways by which potentially protective antibody concentrations against pneumococci could be achieved in early infancy. The aim of this thesis is to increase the knowledge of antibody mediated protection against pneumococcal disease in infants and young children. We investigated the transfer of maternal anti-pneumococcal antibodies from Filipino mothers to their infants, the persistence of the transferred antibodies in the infants, the immunogenicity of the 23-valent pneumococcal polysaccharide vaccine (PPV) in infants and the response of the children to a second dose of PPV at three years of age. We also investigated the development of antibodies to pneumococcal protein antigens in relation to culture-confirmed pneumococcal carriage in infants. Serum samples were collected from the mothers, the umbilical cords and from the infants at young age as well as at three years of age. The samples were used to determine the antibody concentrations to pneumococcal serotypes 1, 5, 6B, 14, 18C and 19F, as well as to the pneumococcal proteins PspA, PsaA, Ply, PspC, PhtD, PhtDC and LytC by the enzyme immunoassay. The findings of the present study confirm previously obtained results and add to the global knowledge of responses to PPV in young children. Immunising pregnant women with PPV provides the infants with increased concentrations of pneumococcal polysaccharide antibodies. Of the six serotypes examined, serotypes 1 and 5 were immunogenic already in infants. At three years of age, the children responded well to the second dose of PPV suggesting that maternal and early infant immunisations might not induce hyporesponsiveness to polysaccharide antigens after subsequent immunisations. The anti-protein antibody findings provide useful information for the development of pneumococcal protein vaccines. All six proteins studied were immunogenic in infancy and the development of anti-protein antibodies started early in life in relation to pneumococcal carriage.

Persistence Problem in Two-Dimensional Fluid Turbulence

We present a natural framework for studying the persistence problem in two-dimensional fluid turbulence by using the Okubo-Weiss parameter Lambda to distinguish between vortical and extensional regions. We then use a direct numerical simulation of the two-dimensional, incompressible Navier-Stokes equation with Ekman friction to study probability distribution functions (PDFs) of the persistence times of vortical and extensional regions by employing both Eulerian and Lagrangian measurements. We find that, in the Eulerian case, the persistence-time PDFs have exponential tails; by contrast, this PDF for Lagrangian particles, in vortical regions, has a power-law tail with an exponent theta = 2.9 +/- 0.2.

Dynamics of zeolite cage and its effect on the diffusion properties of sorbate: persistence of diffusion anomaly in NaA zeolite

Recent computer simulations on zeolites Y and A have found that the diffusion coefficient and the rate of intercage diffusion exhibit, apart from a linear dependence on the reciprocal of the square of the sorbate diameter, an anomalous peak as sorbate diameter approaches the window diameter. Here we report molecular dynamics simulations of zeolite NaA incorporating framework flexibility as a function of sorbate diameter in order to verify the existence of anomalous diffusion. Results suggest persistence of anomalous diffusion or ring effect. This suggests that the anomalous behavior is a general effect characteristic of zeolites Y and A. The barrier for diffusion across the eight-ring window is seen to be negative and is found to decrease with sorbate size. The effect of sorbate on the cage motion has also been investigated. Results suggest that the window expands during intercage migration only if the sorbate size is comparable to the window diameter. Flexible cage simulations yield a higher value for the diffusion coefficient and also the rate of intercage diffusion. This increase has been shown to be due to an increase in the intercage diffusions via the centralized diffusion mode rather than the surface-mediated mode. It is shown that this increase arises from an increase in the single particle density distribution in the region near the cage center.

Additional role for the ccd operon of F-plasmid as a transmissible persistence factor

Toxin-antitoxin (TA) systems are found on both bacterial plasmids and chromosomes, but in most cases their functional role is unclear. Gene knockouts often yield limited insights into functions of individual TA systems because of their redundancy. The well-characterized F-plasmid-based CcdAB TA system is important for F-plasmid maintenance. We have isolated several point mutants of the toxin CcdB that fail to bind to its cellular target, DNA gyrase, but retain binding to the antitoxin, CcdA. Expression of such mutants is shown to result in release of the WT toxin from a functional preexisting TA complex as well as derepression of the TA operon. One such inactive, active-site mutant of CcdB was used to demonstrate the contribution of CcdB to antibiotic persistence. Transient activation of WT CcdB either by coexpression of the mutant or by antibiotic/heat stress was shown to enhance the generation of drug-tolerant persisters in a process dependent on Lon protease and RecA. An F-plasmid containing a ccd locus can, therefore, function as a transmissible persistence factor.

Quorum sensing and pathogenesis: role of small signalling molecules in bacterial persistence

The pathogenesis of Mycobacterium tuberculosis is associated with its ability to survive inside the human host and the bacteria use a variety of mechanism to evade the host's defence. A clearer understanding of the host pathogen interaction is needed to follow the pathogenicity and virulence. Recent advances in the study of inter and intra-cellular communication in bacteria had prompted us to study the role of quorum sensing in bacterial survival and pathogenicity. The cell cell communication in bacteria (quorum sensing) is mediated through the exchange of small molecules called as autoinducers that allow bacteria to modulate their gene expression in response to change in cell-population density. It is a coordinated response that confers multicellularity to a bacterial population in response to stress from external environment. Quorum sensing molecules are the global regulators and regulate a wide range of physiological processes including biofilm formation, motility, cell differentiation, long-term survival and many others. Many bacterial pathogens require quorum sensing to produce the virulence factors in response to host pathogen interaction. Here, we summarize our current understanding on small molecule signalling and their role in the bacterial persistence. New discoveries in these areas have enriched our knowledge on intracellular signalling and their role in the long-term survival of mycobacteria under nutrient starvation.

Effects of initial height on the steady-state persistence probability of linear growth models

The effects of the initial height on the temporal persistence probability of steady-state height fluctuations in up-down symmetric linear models of surface growth are investigated. We study the (1 + 1)-dimensional Family model and the (1 + 1)-and (2 + 1)-dimensional larger curvature (LC) model. Both the Family and LC models have up-down symmetry, so the positive and negative persistence probabilities in the steady state, averaged over all values of the initial height h(0), are equal to each other. However, these two probabilities are not equal if one considers a fixed nonzero value of h(0). Plots of the positive persistence probability for negative initial height versus time exhibit power-law behavior if the magnitude of the initial height is larger than the interface width at saturation. By symmetry, the negative persistence probability for positive initial height also exhibits the same behavior. The persistence exponent that describes this power-law decay decreases as the magnitude of the initial height is increased. The dependence of the persistence probability on the initial height, the system size, and the discrete sampling time is found to exhibit scaling behavior.

New Keynesian Model Features that Can Reproduce Lead, Lag and Persistence Patterns

This paper uses a new method for describing dynamic comovement and persistence in economic time series which builds on the contemporaneous forecast error method developed in den Haan (2000). This data description method is then used to address issues in New Keynesian model performance in two ways. First, well known data patterns, such as output and inflation leads and lags and inflation persistence, are decomposed into forecast horizon components to give a more complete description of the data patterns. These results show that the well known lead and lag patterns between output and inflation arise mostly in the medium term forecasts horizons. Second, the data summary method is used to investigate a rich New Keynesian model with many modeling features to see which of these features can reproduce lead, lag and persistence patterns seen in the data. Many studies have suggested that a backward looking component in the Phillips curve is needed to match the data, but our simulations show this is not necessary. We show that a simple general equilibrium model with persistent IS curve shocks and persistent supply shocks can reproduce the lead, lag and persistence patterns seen in the data.