Shear stress paradigm for perinatal fractal arterial network remodeling in lambs with pulmonary hypertension and increased pulmonary blood flow

Congenital heart disease with increased blood flow commonly leads to the development of increased pulmonary vascular reactivity and pulmonary arterial hypertension by mechanisms that remain unclear. We hypothesized a shear stress paradigm of hemodynamic reactivity and network remodeling via the persistence and/or exacerbation of a fetal diameter bifurcation phenotype [parent diameter d(0) and daughters d(1) >or= d(2) with alpha < 2 in (d(1)/d(0))(alpha) + (d(2)/d(0))(alpha) and area ratio beta < 1 in beta = (d(1)(2)+ d(2)(2))/ d(0)(2)] that mechanically acts as a high resistance magnifier/shear stress amplifier to blood flow. Evidence of a hemodynamic influence on network remodeling was assessed with a lamb model of high-flow-induced secondary pulmonary hypertension in which an aortopulmonary graft was surgically placed in one twin in utero (Shunt twin) but not in the other (Control twin). Eight weeks after birth arterial casts were made of the left pulmonary arterial circulation. Bifurcation diameter measurements down to 0.010 mm in the Shunt and Control twins were then compared with those of an unoperated fetal cast. Network organization, cumulative resistance, and pressure/shear stress distributions were evaluated via a fractal model whose dimension D(0) approximately alpha delineates hemodynamic reactivity. Fetus and Control twin D(0) differed: fetus D(0)=1.72, a high-resistance/shear stress amplifying condition; control twin D(0) = 2.02, an area-preserving transport configuration. The Shunt twin (D(0)=1.72) maintained a fetal design but paradoxically remodeled diameter geometry to decrease cumulative resistance relative to the Control twin. Our results indicate that fetal/neonatal pulmonary hemodynamic reactivity remodels in response to shear stress, but the response to elevated blood flow and pulmonary hypertension involves the persistence and exacerbation of a fetal diameter bifurcation phenotype that facilitates endothelial dysfunction/injury.     

Can the invasive European rabbit (Oryctolagus cuniculus) assume the soil engineering role of locally-extinct natives?

Habitat modifying species can play crucial roles in ecosystem function. Invasive engineers may assume these roles where native engineers have been lost from the system. We compared the dynamics of the foraging pits of an invasive engineer, the European rabbit (Oryctolagus cuniculus) with two native mammals, the greater bilby (Macrotis lagotis) and the burrowing bettong (Bettongia lesueur). Foraging pits are small surface depressions created by animals when they forage for seeds, bulbs, roots, invertebrates and fungi. We measured foraging pit density and turnover, and density and richness of plant seedlings in pits and adjacent surfaces across three landforms representing a gradient in resource availability inside (bilbies and bettongs), and outside (rabbits only) a reserve in an arid Australian shrubland over 2 years. Pits of the native engineers contained 80% more seedlings (11.2 plants m⁻²) than rabbit pits (6.22 plants m⁻²). Further, rabbit pits supported 3.6-times fewer seedlings than equivalent non-pit surfaces outside the exclosure. Only one plant species was restricted entirely to pits. The reserve had more foraging pits and greater turnover than outside, but contrary to prediction, pit effects on seedling density were no greater in the more resource-limited dunes. There were some strong temporal and landscape effects on pit density and species composition, but generally trends were similar inside and outside the reserve. Overall, despite their functional similarities, invasive rabbits created fewer pits that were less favourable patches for seedlings than those of native engineers. Our work suggests that a suite of ecosystem processes associated with fertile patch creation has potentially been lost with the extirpation of bilbies and bettongs.     

Effects of climate legacies on above‐ and belowground community assembly

The role of climatic legacies in regulating community assembly of above‐ and belowground species in terrestrial ecosystems remains largely unexplored and poorly understood. Here, we report on two separate regional and continental empirical studies, including >500 locations, aiming to identify the relative importance of climatic legacies (climatic anomaly over the last 20,000 years) compared to current climates in predicting the relative abundance of ecological clusters formed by species strongly co‐occurring within two independent above‐ and belowground networks. Climatic legacies explained a significant portion of the variation in the current community assembly of terrestrial ecosystems (up to 15.4%) that could not be accounted for by current climate, soil properties, and management. Changes in the relative abundance of ecological clusters linked to climatic legacies (e.g., past temperature) showed the potential to indirectly alter other clusters, suggesting cascading effects. Our work illustrates the role of climatic legacies in regulating ecosystem community assembly and provides further insights into possible winner and loser community assemblies under global change scenarios.     

Significant patterns of population genetic structure and limited gene flow in a threatened macropodid marsupial despite continuous habitat in southeast Queensland, Australia

Many endangered species worldwide are found in remnant populations, often within fragmented landscapes. However, when possible, an understanding of the natural extent of population structure and dispersal behaviour of threatened species would assist in their conservation and management. The brush-tailed rock-wallaby (Petrogale penicillata), a once abundant and widespread rock-wallaby species across southeastern Australia, has become nearly extinct across much of the southern part of its range. However, the northern part of the species’ range still sustains many small colonies closely distributed across suitable habitat, providing a rare opportunity to investigate the natural population dynamics of a listed threatened species. We used 12 microsatellite markers to investigate genetic diversity, population structure and gene flow among brush-tailed rock-wallaby colonies within and among two valley regions with continuous habitat in southeast Queensland. We documented high and significant levels of population genetic structure between rock-wallaby colonies embedded in continuous escarpment habitat and forest. We found a strong and significant pattern of isolation-by-distance among colonies indicating restricted gene flow over a small geographic scale ( <10 km) and conclude that gene flow is more likely limited by intrinsic factors rather than environmental factors. In addition, we provide evidence that genetic diversity was significantly lower in colonies located in a more isolated valley region compared to colonies located in a valley region surrounded by continuous habitat. These findings shed light on the processes that have resulted in the endangered status of rock-wallaby species in Australia and they have strong implications for the conservation and management of both the remaining ‘connected’8 brush-tailed rock-wallaby colonies in the northern parts of the species’8 range and the remnant endangered populations in the south.     

Nematode community structure in the brush-tailed rock-wallaby, Petrogale penicillata: Implications of captive breeding and the translocation of wildlife

Despite an increasing appreciation of the disease risks associated with wild-life translocations, the effects which captive breeding programs exert on parasite communities remain understudied. This may be attributed, in part, to the current lack of rapid and cost-effective techniques for comparing parasite assemblages between host populations. Terminal restriction fragment length polymorphism (T-RFLP) analysis of the rDNA region encompassing the internal transcribed spacers (ITS-1 and ITS-2) and 5.8S rRNA gene was used to characterise bursate nematode communities (suborder Strongylida) across two captive and two non-captive colonies of the threatened brush-tailed rock-wallaby, Petrogale penicillata. A clone library was constructed and a restriction enzyme selected to differentiate the predominant operational taxonomic units (OTUs) by the unique peak profiles they generated. The prevalence, intensity of infection and comparative structure of strongylid assemblages was evaluated for each of the host colonies. Compared to wild conspecifics, captive wallabies exhibited a reduced prevalence of infection and significantly lower faecal egg counts. T-RFLP revealed that a high proportion of the OTUs co-occurred across three of the four study locations. Despite this, the composition of strongylid assemblages was significantly different between the colonies, even when host translocation events had occurred. These results suggest that captive breeding programs may exert a profound impact on parasitic helminth assemblages. Developing efficient techniques for characterising community dynamics in potentially pathogenic organisms is critical to the long term success of species recovery efforts worldwide.     

Novel insights into the phylogenetic relationships of the endangered marsupial genus Potorous

The three extant potoroo species of the marsupial genus Potorous -Potorous tridactylus, P. longipes and P. gilbertii - are all of conservation concern due to introduced predators and habitat loss associated with the European settlement of Australia. Robust phylogenies can be useful to inform conservation management, but past phylogenetic studies on potoroos have been unable to fully resolve relationships within the genus. Here, a multi-locus approach was employed, using three mitochondrial DNA (mtDNA): NADH dehydrogenase subunit 2, cytochrome c oxidase subunit 1 and 12S rRNA and four nuclear DNA (nuDNA) gene regions: breast and ovarian cancer susceptibility gene, recombination activating gene-1, apolipoprotein B and omega globin. This was coupled with widespread geographic sampling of the broadly distributed P. tridactylus, to investigate the phylogenetic relationships within this genus. Analyses of the mtDNA identified five distinct and highly divergent lineages including, P. longipes, P. gilbertii and three distinct lineages within P. tridactylus (northern mainland, southern mainland and Tasmanian). P. tridactylus was paraphyletic with the P. gilbertii lineage, suggesting that cryptic taxa may exist within P. tridactylus. NuDNA sequences lacked the resolution of mtDNA. Although they resolved the three currently recognised species, they were unable to differentiate lineages within P. tridactylus. Current management of P. tridactylus as two sub-species (mainland and Tasmania) does not recognise the full scope of genetic diversity within this species, especially that of the mainland populations. Until data from more informative nuDNA markers are available, we recommend this species be managed as the following three subspecies: Potorous tridactylus tridactylus (southern Queensland and northern New South Wales); Potorous tridactylus trisulcatus (southern New South Wales and Victoria) Potorous tridactylus apicalis (Tasmania). Molecular dating estimated that divergences within Potorous occurred in the late Miocene through to the early Pliocene.     

The biology and future prospects of antivirulence therapies

The emergence and increasing prevalence of bacterial strains that are resistant to available antibiotics demand the discovery of new therapeutic approaches. Targeting bacterial virulence is an alternative approach to antimicrobial therapy that offers promising opportunities to inhibit pathogenesis and its consequences without placing immediate life-or-death pressure on the target bacterium. Certain virulence factors have been shown to be potential targets for drug design and therapeutic intervention, whereas new insights are crucial for exploiting others. Targeting virulence represents a new paradigm to empower the clinician to prevent and treat infectious diseases.     

Internal and external validity of cluster randomised trials: systematic review of recent trials

Objectives To assess aspects of the internal validity of recently published cluster randomised trials and explore the reporting of information useful in assessing the external validity of these trials.Design Review of 34 cluster randomised trials in primary care published in 2004 and 2005 in seven journals (British Medical Journal, British Journal of General Practice, Family Practice, Preventive Medicine, Annals of Internal Medicine, Journal of General Internal Medicine, Pediatrics).Data sources National Library of Medicine (Medline) via PubMed.Data extraction To assess aspects of internal validity we extracted data on appropriateness of sample size calculations and analyses, methods of identifying and recruiting individual participants, and blinding. To explore reporting of information useful in assessing external validity we extracted data on cluster eligibility, cluster inclusion and retention, cluster generalisability, and the feasibility and acceptability of the intervention to health providers in clusters.Results 21 (62%) trials accounted for clustering in sample size calculations and 30 (88%) in the analysis; about a quarter were potentially biased because of procedures surrounding recruitment and identification of patients; individual participants were blind to allocation status in 19 (56%) and outcome assessors were blind in 15 (44%). In almost half the reports, information relating to generalisability of clusters was poorly reported, and in two fifths there was no information about the feasibility and acceptability of the intervention.Conclusions Cluster randomised trials are essential for evaluating certain types of interventions. Issues affecting their internal validity, such as appropriate sample size calculations and analysis, have been widely disseminated and are now better addressed by researchers. Blinding of those identifying and recruiting patients to allocation status is recommended but is not always carried out. There may be fewer barriers to internal validity in trials in which individual participants are not recruited. External validity seems poorly addressed in many trials, yet is arguably as important as internal validity in judging quality as a basis for healthcare intervention.