Time series analysis of RSV and bronchiolitis seasonality in temperate and tropical Western Australia.

Respiratory syncytial virus (RSV) causes respiratory illness in young children and is most commonly associated with bronchiolitis. RSV typically occurs as annual or biennial winter epidemics in temperate regions, with less pronounced seasonality in the tropics. We sought to characterise and compare the seasonality of RSV and bronchiolitis in temperate and tropical Western Australia. We examined over 13 years of RSV laboratory identifications and bronchiolitis hospitalisations in children, using an extensive linked dataset from Western Australia. We applied mathematical time series analyses to identify the dominant seasonal cycle, and changes in epidemic size and timing over this period. Both the RSV and bronchiolitis data showed clear winter epidemic peaks in July or August in the southern Western Australia regions, but less identifiable seasonality in the northern regions. Use of complex demodulation proved very effective at comparing disease epidemics. The timing of RSV and bronchiolitis epidemics coincided well, but the size of the epidemics differed, with more consistent peak sizes for bronchiolitis than for RSV. Our results show that bronchiolitis hospitalisations are a reasonable proxy for the timing of RSV detections, but may not fully capture the magnitude of RSV epidemics.

Exploring the dynamics of respiratory syncytial virus (RSV) transmission in children.

Respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in children. Whilst highly seasonal, RSV dynamics can have either one-year (annual) or two-year (biennial) cycles. Furthermore, some countries show a 'delayed biennial' pattern, where the epidemic peak in low incidence years is delayed. We develop a compartmental model for RSV infection, driven by a seasonal forcing function, and conduct parameter space and bifurcation analyses to document parameter ranges that give rise to these different seasonal patterns. The model is sensitive to the birth rate, transmission rate, and seasonality parameters, and can replicate RSV dynamics observed in different countries. The seasonality parameter must exceed a threshold for the model to produce biennial cycles. Intermediate values of the birth rate produce the greatest delay in these biennial cycles, while the model reverts to annual cycles if the duration of immunity is too short. Finally, the existence of period doubling and period halving bifurcations suggests robust model dynamics, in agreement with the known regularity of RSV outbreaks. These findings help explain observed RSV data, such as regular biennial dynamics in Western Australia, and delayed biennial dynamics in Finland. From a public health perspective, our findings provide insight into the drivers of RSV transmission, and a foundation for exploring RSV interventions.

Dawn and Dusk Set States of the Circadian Oscillator in Sprouting Barley (Hordeum vulgare) Seedlings.

The plant circadian clock is an internal timekeeper that coordinates biological processes with daily changes in the external environment. The transcript levels of clock genes, which oscillate to control circadian outputs, were examined during early seedling development in barley (Hordeum vulgare), a model for temperate cereal crops. Oscillations of clock gene transcript levels do not occur in barley seedlings grown in darkness or constant light but were observed with day-night cycles. A dark-to-light transition influenced transcript levels of some clock genes but triggered only weak oscillations of gene expression, whereas a light-to-dark transition triggered robust oscillations. Single light pulses of 6, 12 or 18 hours induced robust oscillations. The light-to-dark transition was the primary determinant of the timing of subsequent peaks of clock gene expression. After the light-to-dark transition the timing of peak transcript levels of clock gene also varied depending on the length of the preceding light pulse. Thus, a single photoperiod can trigger initiation of photoperiod-dependent circadian rhythms in barley seedlings. Photoperiod-specific rhythms of clock gene expression were observed in two week old barley plants. Changing the timing of dusk altered clock gene expression patterns within a single day, showing that alteration of circadian oscillator behaviour is amongst the most rapid molecular responses to changing photoperiod in barley. A barley EARLY FLOWERING3 mutant, which exhibits rapid photoperiod-insensitive flowering behaviour, does not establish clock rhythms in response to a single photoperiod. The data presented show that dawn and dusk cues are important signals for setting the state of the circadian oscillator during early development of barley and that the circadian oscillator of barley exhibits photoperiod-dependent oscillation states.

How is FLC repression initiated by cold?

Vernalization is the promotion of flowering in response to prolonged exposure to low temperatures. In Arabidopsis, FLOWERING LOCUS C (FLC), a suppressor of flowering, is repressed by low temperatures but the mechanism leading to the initial decrease in FLC transcription remains a mystery. No mutants that block the repression of FLC at low temperatures have been identified to date. If the failure to identify such a mutant is assumed to imply that no such mutant exists, then it follows that the first response to the drop in temperature is physical, not genetic. In this Opinion article we propose that the drop in temperature first causes a simple change in the topology of the chromatin polymer, which in turn initiates the repression of FLC transcription.

Information recovery in molecular biology: causal modelling of regulated promoter switching experiments.

The recovery of information from indirect measurements takes different forms depending on the sophistication with which the process being researched can be modelled mathematically. The forms range from (1) the historical and classical inverse problems regularization situation where explicit models which guaranteed existence and uniqueness have been formulated, through (2) situations where model formulation is performed implicitly as a calibration-and-prediction ansatz, to (3) the exploratory (biology) situation where the underlying mechanism is unknown and constraining information about its dynamics is being sought through appropriate experimentation. Each represents a different aspect of the solution of inverse problems. It is the nature of the exploratory form that is discussed in this paper. The focus is the causal modelling of regulated promoter switching experiments performed to understand the dynamics of the genetic control of various biological developmental processes such as vernalization in plants; in particular, regulated promoter switching experiments used to examine the relationship between FLC transcription activity and the associated histone H3 lysine 27 trimethylation at a vernalization-responsive gene in plants. Using a causal representation with Kohlrausch function fading memory, it is shown how such modelling can be used to quantitatively assess the closeness of the linking of one biological process with another, and, in particular, to conclude that the dynamics of FLC transcription and associated H3K27me3 activity are closely linked biologically.

Modeling antiviral resistance in plants.

The goal of this chapter is to describe in simple terms how the use of ordinary differential equation (ODE) modeling, in conjunction with experimentation, can be utilized to improve our understanding of the dynamics of gene silencing and virus resistance in plants.

Molecular classification of barley (Hordeum vulgare L.) mutants using derivative NIR spectroscopy.

Near-infrared reflectance (NIR) spectroscopy was used in the characterization of grain morphology mutants of barley ( Hordeum vulgare L.) in relation to grain nitrogen (N) content and protein composition. Derivative spectroscopy provided spectra with enhanced resolution, allowing wavelengths to be identified with clear differences in contribution from associated chemical bonds. Comparisons of fourth-derivative spectra of wholemeal flour from high-N grains with flour from low-N grains identified wavelengths at which there were statistically significant differences between the groups. Their importance was independently confirmed by step-up regression using these wavelengths to generate an equation predicting N content (R(2) = 0.98). Fourth-derivative spectral comparisons also allowed novel biochemical differences to be predicted. Visual assessment of the spectra of all mutants revealed a variable region (1470-1520 nm, corresponding to N-H stretch vibrations) that allowed two extreme sets to be defined. The protein extracted from these two sets differed markedly in hordein content.