Somatostatin neuron contributions to cortical slow wave dysfunction in adult mice exposed to developmental ethanol.

Introduction: Transitions between sleep and waking and sleep-dependent cortical oscillations are heavily dependent on GABAergic neurons. Importantly, GABAergic neurons are especially sensitive to developmental ethanol exposure, suggesting a potential unique vulnerability of sleep circuits to early ethanol. In fact, developmental ethanol exposure can produce long-lasting impairments in sleep, including increased sleep fragmentation and decreased delta wave amplitude. Here, we assessed the efficacy of optogenetic manipulations of somatostatin (SST) GABAergic neurons in the neocortex of adult mice exposed to saline or ethanol on P7, to modulate cortical slow-wave physiology. Methods: SST-cre × Ai32 mice, which selectively express channel rhodopsin in SST neurons, were exposed to ethanol or saline on P7. This line expressed similar developmental ethanol induced loss of SST cortical neurons and sleep impairments as C57BL/6By mice. As adults, optical fibers were implanted targeting the prefrontal cortex (PFC) and telemetry electrodes were implanted in the neocortex to monitor slow-wave activity and sleep-wake states. Results: Optical stimulation of PFC SST neurons evoked slow-wave potentials and long-latency single-unit excitation in saline treated mice but not in ethanol mice. Closed-loop optogenetic stimulation of PFC SST neuron activation on spontaneous slow-waves enhanced cortical delta oscillations, and this manipulation was more effective in saline mice than P7 ethanol mice. Discussion: Together, these results suggest that SST cortical neurons may contribute to slow-wave impairment after developmental ethanol.

Development of a mechanistic dengue simulation model for Guangzhou.

Dengue infection in China has increased dramatically in recent years. Guangdong province (main city Guangzhou) accounted for more than 94% of all dengue cases in the 2014 outbreak. Currently, there is no existing effective vaccine and most efforts of control are focused on the vector itself. This study aimed to evaluate different dengue management strategies in a region where this disease is emerging. This work was done by establishing a dengue simulation model for Guangzhou to enable the testing of control strategies aimed at vector control and vaccination. For that purpose, the computer-based dengue simulation model (DENSiM) together with the Container-Inhabiting Mosquito Simulation Model (CIMSiM) has been used to create a working dengue simulation model for the city of Guangzhou. In order to achieve the best model fit against historical surveillance data, virus introduction scenarios were run and then matched against the actual dengue surveillance data. The simulation model was able to predict retrospective outbreaks with a sensitivity of 0.18 and a specificity of 0.98. This new parameterisation can now be used to evaluate the potential impact of different control strategies on dengue transmission in Guangzhou. The knowledge generated from this research would provide useful information for authorities regarding the historic patterns of dengue outbreaks, as well as the effectiveness of different disease management strategies.

Evolution of morphology and locomotor performance in anurans: relationships with microhabitat diversification.

The relationships between morphology, performance, behavior and ecology provide evidence for multiple and complex phenotypic adaptations. The anuran body plan, for example, is evolutionarily conserved and shows clear specializations to jumping performance back at least to the early Jurassic. However, there are instances of more recent adaptation to habit diversity in the post-cranial skeleton, including relative limb length. The present study tested adaptive models of morphological evolution in anurans associated with the diversity of microhabitat use (semi-aquatic arboreal, fossorial, torrent, and terrestrial) in species of anuran amphibians from Brazil and Australia. We use phylogenetic comparative methods to determine which evolutionary models, including Brownian motion (BM) and Ornstein-Uhlenbeck (OU) are consistent with morphological variation observed across anuran species. Furthermore, this study investigated the relationship of maximum distance jumped as a function of components of morphological variables and microhabitat use. We found there are multiple optima of limb lengths associated to different microhabitats with a trend of increasing hindlimbs in torrent, arboreal, semi-aquatic whereas fossorial and terrestrial species evolve toward optima with shorter hindlimbs. Moreover, arboreal, semi-aquatic and torrent anurans have higher jumping performance and longer hindlimbs, when compared to terrestrial and fossorial species. We corroborate the hypothesis that evolutionary modifications of overall limb morphology have been important in the diversification of locomotor performance along the anuran phylogeny. Such evolutionary changes converged in different phylogenetic groups adapted to similar microhabitat use in two different zoogeographical regions.

Projections of increased and decreased dengue incidence under climate change.

Dengue is the world's most prevalent mosquito-borne disease, with more than 200 million people each year becoming infected. We used a mechanistic virus transmission model to determine whether climate warming would change dengue transmission in Australia. Using two climate models each with two carbon emission scenarios, we calculated future dengue epidemic potential for the period 2046-2064. Using the ECHAM5 model, decreased dengue transmission was predicted under the A2 carbon emission scenario, whereas some increases are likely under the B1 scenario. Dengue epidemic potential may decrease under climate warming due to mosquito breeding sites becoming drier and mosquito survivorship declining. These results contradict most previous studies that use correlative models to show increased dengue transmission under climate warming. Dengue epidemiology is determined by a complex interplay between climatic, human host, and pathogen factors. It is therefore naive to assume a simple relationship between climate and incidence, and incorrect to state that climate warming will uniformly increase dengue transmission, although in general the health impacts of climate change will be negative.

Improving public health intervention for mosquito-borne disease: the value of geovisualization using source of infection and LandScan data.

Epidemiological studies use georeferenced health data to identify disease clusters but the accuracy of this georeferencing is obfuscated by incorrectly assigning the source of infection and by aggregating case data to larger geographical areas. Often, place of residence (residence) is used as a proxy for the source of infection (source) which may not be accurate. Using a 21-year dataset from South Australia of human infections with the mosquito-borne Ross River virus, we found that 37% of cases were believed to have been acquired away from home. We constructed two risk maps using age-standardized morbidity ratios (SMRs) calculated using residence and patient-reported source. Both maps confirm significant inter-suburb variation in SMRs. Areas frequently named as the source (but not residence) and the highest-risk suburbs both tend to be tourist locations with vector mosquito habitat, and camping or outdoor recreational opportunities. We suggest the highest-risk suburbs as places to focus on for disease control measures. We also use a novel application of ambient population data (LandScan) to improve the interpretation of these risk maps and propose how this approach can aid in implementing disease abatement measures on a smaller scale than for which disease data are available.

Desiccation survival time for eggs of a widespread and invasive Australian mosquito species, Aedes (Finlaya) notoscriptus (Skuse).

The Australian native mosquito Aedes (Finlaya) notoscriptus (Skuse) is closely associated with natural and artificial water holding receptacles. Eggs are laid in habitats where they are exposed to drying conditions as water levels fluctuate. Withstanding desiccation enables survival in challenging environments and increases the potential for establishment in non-native habitats. Until now, the desiccation resistance of Ae. notoscriptus eggs has been unknown despite the historical invasive success of this important dog heartworm and arbovirus vector. Viability and mean survival times of eggs from two Ae. notoscriptus populations (metropolitan areas of Sydney, NSW and Adelaide, SA) were evaluated, with eggs stored under three dryness conditions for up to 367 days. Our results revealed that Ae. notoscriptus eggs can withstand desiccation for extended periods, under a variety of conditions, with approximately 9-13% egg viability recorded after one year. This prolonged egg survival reflects the widespread distribution of this mosquito in Australia and its history of incursions and subsequent establishment in non-native habitats. Differences in mean egg volume were recorded in addition to significantly different egg length to width ratios for the two populations, which may reflect adaptation to biotope of origin and an associated likelihood of drought and drying conditions. The results of this study suggest that the desiccation resistant eggs of Ae. notoscriptus make this species highly adaptable, increasing the risk of movement to non-endemic regions of the world.

Effects of Cohabitation on the Population Performance and Survivorship of the Invasive Mosquito Aedes albopictus and the Resident Mosquito Aedes notoscriptus (Diptera: Culicidae) in Australia.

The presence of Aedes albopictus (Skuse) in the Torres Strait of northern Australia increases the potential for colonization and establishment on the mainland. However, there is a possibility that native species that occupy the same habitats may influence the population performance of Ae. albopictus, potentially affecting the establishment of this species in Australia. Cohabitation experiments were performed with the endemic Aedes notoscriptus (Skuse), which has been found occupying the same larval habitats as Ae. albopictus in the Torres Strait and is the most widespread container-inhabiting Aedes species in Australia. The influence of environmental factors and cohabitation between the two species was examined using different climates, food resource levels, food resource types, and species densities. Survivorship proportions and a population performance index (λ') were calculated and compared. The consequences of increased Ae. notoscriptus densities were reduced survivorship and λ' for Ae. albopictus. Despite this, the mean λ' of Ae. albopictus and Ae. notoscriptus was consistently ≥ 1.06, indicating both species could increase under all conditions, potentially due to increasing conspecific densities negatively affecting Ae. notoscriptus. The outcomes from this study suggest that the preexisting presence of Ae. notoscriptus may not prevent the establishment of Ae. albopictus in Australia.

Testing the impact of virus importation rates and future climate change on dengue activity in Malaysia using a mechanistic entomology and disease model.

We aimed to reparameterize and validate an existing dengue model, comprising an entomological component (CIMSiM) and a disease component (DENSiM) for application in Malaysia. With the model we aimed to measure the effect of importation rate on dengue incidence, and to determine the potential impact of moderate climate change (a 1 °C temperature increase) on dengue activity. Dengue models (comprising CIMSiM and DENSiM) were reparameterized for a simulated Malaysian village of 10 000 people, and validated against monthly dengue case data from the district of Petaling Jaya in the state of Selangor. Simulations were also performed for 2008-2012 for variable virus importation rates (ranging from 1 to 25 per week) and dengue incidence determined. Dengue incidence in the period 2010-2012 was modelled, twice, with observed daily weather and with a 1 °C increase, the latter to simulate moderate climate change. Strong concordance between simulated and observed monthly dengue cases was observed (up to r = 0·72). There was a linear relationship between importation and incidence. However, a doubling of dengue importation did not equate to a doubling of dengue activity. The largest individual dengue outbreak was observed with the lowest dengue importation rate. Moderate climate change resulted in an overall decrease in dengue activity over a 3-year period, linked to high human seroprevalence early on in the simulation. Our results suggest that moderate reductions in importation with control programmes may not reduce the frequency of large outbreaks. Moderate increases in temperature do not necessarily lead to greater dengue incidence.

Mechanistic modeling of sulfur-deprived photosynthesis and hydrogen production in suspensions of Chlamydomonas reinhardtii.

The ability of unicellular green algal species such as Chlamydomonas reinhardtii to produce hydrogen gas via iron-hydrogenase is well known. However, the oxygen-sensitive hydrogenase is closely linked to the photosynthetic chain in such a way that hydrogen and oxygen production need to be separated temporally for sustained photo-production. Under illumination, sulfur-deprivation has been shown to accommodate the production of hydrogen gas by partially-deactivating O2 evolution activity, leading to anaerobiosis in a sealed culture. As these facets are coupled, and the system complex, mathematical approaches potentially are of significant value since they may reveal improved or even optimal schemes for maximizing hydrogen production. Here, a mechanistic model of the system is constructed from consideration of the essential pathways and processes. The role of sulfur in photosynthesis (via PSII) and the storage and catabolism of endogenous substrate, and thus growth and decay of culture density, are explicitly modeled in order to describe and explore the complex interactions that lead to H2 production during sulfur-deprivation. As far as possible, functional forms and parameter values are determined or estimated from experimental data. The model is compared with published experimental studies and, encouragingly, qualitative agreement for trends in hydrogen yield and initiation time are found. It is then employed to probe optimal external sulfur and illumination conditions for hydrogen production, which are found to differ depending on whether a maximum yield of gas or initial production rate is required. The model constitutes a powerful theoretical tool for investigating novel sulfur cycling regimes that may ultimately be used to improve the commercial viability of hydrogen gas production from microorganisms.

Productivity and population density estimates of the dengue vector mosquito Aedes aegypti (Stegomyia aegypti) in Australia.

New mosquito control strategies centred on the modifying of populations require knowledge of existing population densities at release sites and an understanding of breeding site ecology. Using a quantitative pupal survey method, we investigated production of the dengue vector Aedes aegypti (L.) (Stegomyia aegypti) (Diptera: Culicidae) in Cairns, Queensland, Australia, and found that garden accoutrements represented the most common container type. Deliberately placed 'sentinel' containers were set at seven houses and sampled for pupae over 10 weeks during the wet season. Pupal production was approximately constant; tyres and buckets represented the most productive container types. Sentinel tyres produced the largest female mosquitoes, but were relatively rare in the field survey. We then used field-collected data to make estimates of per premises population density using three different approaches. Estimates of female Ae. aegypti abundance per premises made using the container-inhabiting mosquito simulation (CIMSiM) model [95% confidence interval (CI) 18.5-29.1 females] concorded reasonably well with estimates obtained using a standing crop calculation based on pupal collections (95% CI 8.8-22.5) and using BG-Sentinel traps and a sampling rate correction factor (95% CI 6.2-35.2). By first describing local Ae. aegypti productivity, we were able to compare three separate population density estimates which provided similar results. We anticipate that this will provide researchers and health officials with several tools with which to make estimates of population densities.

Regulation of virus neutralization and the persistent fraction by TRIM21.

Despite a central role in immunity, antibody neutralization of virus infection is poorly understood. Here we show how the neutralization and persistence of adenovirus type 5, a prevalent nonenveloped human virus, are dependent upon the intracellular antibody receptor TRIM21. Cells with insufficient amounts of TRIM21 are readily infected, even at saturating concentrations of neutralizing antibody. Conversely, high TRIM21 expression levels decrease the persistent fraction of the infecting virus and allows neutralization by as few as 1.6 antibody molecules per virus. The direct interaction between TRIM21 and neutralizing antibody is essential, as single-point mutations within the TRIM21-binding site in the Fc region of a potently neutralizing antibody impair neutralization. However, infection at high multiplicity can saturate TRIM21 and overcome neutralization. These results provide insight into the mechanism and importance of a newly discovered, effector-driven process of antibody neutralization of nonenveloped viruses.

Eggs of the Australian saltmarsh mosquito, Aedes camptorhynchus, survive for long periods and hatch in instalments: implications for biosecurity in New Zealand.

The Australian saltmarsh mosquito, Aedes camptorhynchus (Diptera: Culicidae), is a significant biting pest and disease vector and is the subject of an eradication programme in New Zealand (NZ), where it has been resident for more than 10 years. To better understand the ecology of this common and widespread pest, we studied egg longevity and hatching patterns in the laboratory. By regularly testing for the presence of viable embryos, we found that eggs may last more than 15 months when stored dry (13% viable at this time). Eggs display instalment hatching, with no more than 56% of a batch hatching upon first inundation. Further hatching may occur for at least six inundations and some unhatched eggs may remain viable even after this. Variation in hatching rates can be observed using different water types, with weaker hatching media stimulating lower hatching rates spread over more inundations. By applying average hatching rates to a non-linear model of natural egg attrition, we showed that egg batches exposed to three inundations should be exhausted (zero live eggs present) in approximately 11 months at the conditions tested here. These findings have implications for the current eradication programme for Ae. camptorhynchus in NZ and for our understanding of the ecology of a widespread and common disease vector in Australia.

Macaque pontine omnipause neurons play no direct role in the generation of eye blinks.

We recorded the activity of pontine omnipause neurons (OPNs) in two macaques during saccadic eye movements and blinks. As previously reported, we found that OPNs fire tonically during fixation and pause about 15 ms before a saccadic eye movement. In contrast, for blinks elicited by air puffs, the OPNs paused <2 ms before the onset of the blink. Thus the burst in the agonist orbicularis oculi motoneurons (OOMNs) and the pause in the antagonist levator palpabrae superioris motoneurons (LPSMNs) necessarily precede the OPN pause. For spontaneous blinks there was no correlation between blink and pause onsets. In addition, the OPN pause continued for 40-60 ms after the time of the maximum downward closing of the eyelids, which occurs around the end of the OOMN burst of firing. LPSMN activity is not responsible for terminating the OPN pause because OPN resumption was very rapid, whereas the resumption of LPSMN firing during the reopening phase is gradual. OPN pause onset does not directly control blink onset, nor does pause offset control or encode the transition between the end of the OOMN firing and the resumption of the LPSMNs. The onset of the blink-related eye transients preceded both blink and OPN pause onsets. Therefore they initiated while the saccadic short-lead burst neurons were still fully inhibited by the OPNs and cannot be saccadic in origin. The abrupt dynamic change of the vertical eye transients from an oscillatory behavior to a single time constant exponential drift predicted the resumption of the OPNs.

Identification of a calcitonin-like diuretic hormone that functions as an intrinsic modulator of the American lobster, Homarus americanus, cardiac neuromuscular system.

In insects, a family of peptides with sequence homology to the vertebrate calcitonins has been implicated in the control of diuresis, a process that includes mixing of the hemolymph. Here, we show that a member of the insect calcitonin-like diuretic hormone (CLDH) family is present in the American lobster, Homarus americanus, serving, at least in part, as a powerful modulator of cardiac output. Specifically, during an ongoing EST project, a transcript encoding a putative H. americanus CLDH precursor was identified; a full-length cDNA was subsequently cloned. In silico analyses of the deduced prepro-hormone predicted the mature structure of the encoded CLDH to be GLDLGLGRGFSGSQAAKHLMGLAAANFAGGPamide (Homam-CLDH), which is identical to a known Tribolium castaneum peptide. RT-PCR tissue profiling suggests that Homam-CLDH is broadly distributed within the lobster nervous system, including the cardiac ganglion (CG), which controls the movement of the neurogenic heart. RT-PCR analysis conducted on pacemaker neuron- and motor neuron-specific cDNAs suggests that the motor neurons are the source of the CLDH message in the CG. Perfusion of Homam-CLDH through the isolated lobster heart produced dose-dependent increases in both contraction frequency and amplitude and a dose-dependent decrease in contraction duration, with threshold concentrations for all parameters in the range 10(-11) to 10(-10) mol l(-1) or less, among the lowest for any peptide on this system. This report is the first documentation of a decapod CLDH, the first demonstration of CLDH bioactivity outside the Insecta, and the first detection of an intrinsic neuropeptide transcript in the crustacean CG.

A lethal ovitrap-based mass trapping scheme for dengue control in Australia: II. Impact on populations of the mosquito Aedes aegypti.

In Cairns, Australia, the impacts on Aedes aegypti L. (Diptera: Culicidae) populations of two types of 'lure & kill' (L&K) lethal ovitraps (LOs), the standard lethal ovitrap (SLO) and the biodegradable lethal ovitrap (BLO) were measured during three mass-trapping interventions. To assess the efficacy of the SLO, two interventions (one dry season and one wet season) were conducted in three discrete areas, each lasting 4 weeks, with the following treatments: (i) SLOs (>200 traps, approximately 4/premise), BG-sentinel traps (BGSs; approximately 15, 1/premise) and larval control (container reduction and methoprene treatment) and (ii) larval control alone, and (iii) untreated control. Female Ae. aegypti populations were monitored for 4 weeks pre- and post-treatment in all three areas using BGSs and sticky ovitraps (SOs) or non-lethal regular ovitraps (ROs). In the dry season, 206 SLOs and 15 BGSs set at 54 and 15 houses, respectively, caught and killed an estimated 419 and 73 female Ae. aegypti, respectively. No significant decrease in collection size of female Ae. aegypti could be attributed to the treatments. In the wet season, 243 SLOs and 15 BGSs killed approximately 993 and 119 female Ae. aegypti, respectively. The mean number of female Ae. aegypti collected after 4 weeks with SOs and BGSs was significantly less than the control (LSD post-hoc test). The third mass-trapping intervention was conducted using the BLO during the wet season in Cairns. For this trial, three treatment areas were each provided with BLOs (>500, approximately 4/premise) plus larval control, and an untreated control area was designated. Adult female Ae. aegypti were collected for 4 weeks pre- and post-treatment using 15 BGSs and 20 SOs. During this period, 53.2% of BLOs contained a total of 6654 Ae. aegypti eggs. Over the intervention period, collections of Ae. aegypti in the treatment areas were significantly less than in the control area for BGSs but not SOs. An influx of relatively large numbers of young females may have confounded the measurement of changes in populations of older females in these studies. This is an important issue, with implications for assessing delayed action control measures, such as LOs and parasites/pathogens that aim to change mosquito age structure. Finally, the high public acceptability of SLOs and BLOs, coupled with significant impacts on female Ae. aegypti populations in two of the three interventions reported here, suggest that mass trapping with SLOs and BLOs can be an effective component of a dengue control strategy.

Modelling the ecology of the coastal mosquitoes Aedes vigilax and Aedes camptorhynchus at Port Pirie, South Australia.

Two mosquito species, Aedes camptorhynchus (Thomson) and Aedes vigilax (Skuse) (Diptera: Culicidae) are responsible for significant nuisance biting and disease transmission in southern coastal Australia. Mosquito abundance, tide height, temperature and rainfall data were collected over three summer seasons (2002, 2003, 2004) at Port Pirie, South Australia and subjected to statistical analysis to develop ecological models for predicting problem mosquito outbreaks. A logistic regression model for Ae. camptorhynchus gave a predictive R(2) of 0.30 using mean air temperature, whereas, for Ae. vigilax, tide height, mean air temperature and day length yielded a regression with an R(2) of 0.68. These models identify significant environmental drivers for both species and may be useful in the prediction of future outbreaks, particularly of Ae. vigilax.

Mosquito repellents in frog skin.

The search for novel insect repellents has been driven by health concerns over established synthetic compounds such as diethyl-m-toluamide (DEET). Given the diversity of compounds known from frog skin and records of mosquito bite and ectoparasite infestation, the presence of mosquito repellents in frogs seemed plausible. We investigated frog skin secretions to confirm the existence of mosquito repellent properties. Litoria caerulea secretions were assessed for mosquito repellency by topical application on mice. The secretions provided protection against host-seeking Culex annulirostris mosquitoes. Olfactometer tests using aqueous washes of skin secretions from L. caerulea and four other frog species were conducted to determine whether volatile components were responsible for repellency. Volatiles from Litoria rubella and Uperoleia mjobergi secretions were repellent to C. annulirostris, albeit not as repellent as a DEET control. The demonstration of endogenous insect repellents in amphibians is novel, and demonstrates that many aspects of frog chemical ecology remain unexplored.

Mark-release-recapture study to measure dispersal of the mosquito Aedes aegypti in Cairns, Queensland, Australia.

In Queensland, Australia, in response to isolated cases of dengue infection, larval control of the vector Aedes aegypti (L.) (Diptera: Culicidae) is targeted at breeding sites within 200 m of a case and interior spraying with a pyrethroid adulticide is targeted at premises within 100 m. To ascertain whether these limits are appropriate, we conducted a mark-release-recapture study to measure the dispersal of female Ae. aegypti in the city of Cairns where transmission occurs. Female mosquitoes reared from wild collected eggs were differentially marked with fluorescent dust depending on whether they were to be released blood-fed or non-blood-fed, and a total of 1,948 females was released. A total of 132 sticky ovitraps was set at 64 premises within a 200 m radius and collections of trapped adults were made at 5-15 days post-release. Sixty-seven females (3.4%) were recaptured, with the furthest being caught 200 m from the release point, and the mean distance travelled was 78 m. Overall, 23.1% of the recaptures outside the release site were taken beyond 100 m by day 15. Dispersal was comparable for both blood-fed and non-blood-fed releases. There was a significant tendency for dispersal to be in a north-westerly direction, probably because of the presence of numerous containers and heavy shading by trees in this direction and a busy road to the south of the release point that appeared to inhibit dispersal. The results suggest that adulticiding may have to be extended beyond 100 m if more than 8 days have elapsed since female Ae. aegypti could have fed upon a viraemic dengue case. The study also shows that dispersal is not random, and that it may be possible to maximize vector control by taking into account environmental factors that affect the direction of female mosquito flight.