Protected biofactors and antioxidants reduce the negative consequences of virus and cold challenge by modulating immunometabolism via changes in the interleukin-6 receptor signaling cascade in the liver.

Protected biofactors and antioxidants (PBA), and protected biofactors and antioxidants with protected organic acids and essential oils (PBA+POAEO) have been shown to have benefits in stressed or challenged birds. Here, we describe the immunometabolic changes observed in the liver of Ross 308 broilers during feed supplementation and brief physiological stress. These studied additives contain protected essential oils, organic acids, and vitamins which may have protective effects on the liver. Thus, we aimed to determine the signaling changes induced by these supplements and the resultant immunometabolic effects in the liver. All birds received a 2X dose of live bronchitis vaccine at d 0 and a 48-h cold challenge by reducing the temperature from 30 to 32°C, to 20 to 23°C on d 3 to 5. Control birds were fed a standard diet without supplementation. Liver samples were collected to evaluate the effects of these treatments on cytokine gene expression and protein phosphorylation via kinome peptide array. ANOVA was used for statistical analysis of the gene expression data (significance at a p-value of 0.05), and PIIKA2 was used for statistical evaluation and comparative analysis of the kinome peptide array data. At d 15, the kinome peptide array analysis and gene expression data showed stimulation of the interleukin 6 receptor (IL-6R) signal transduction for host protection via heightened immune response while inducing immune modulation and reducing inflammation in both supplement treated groups. Significant changes were observed via IL-6R signaling in the metabolic profiles of both groups compared to control and no significant differences when compared to each other. In the liver, these 2 feed additives induced immunometabolic changes predominantly via the IL-6 receptor family signaling cascade. Differences between the 2 treated groups were predominantly in the metabolic pathways, centered around the mTOR pathway and the proteins AMPK, mTOR and S6K, with a more anabolic phenotype following the addition of essential oils.

Ecosystem engineering by digging mammals: effects on soil fertility and condition in Tasmanian temperate woodland.

Many small- and medium-sized mammals dig for their food. This activity potentially affects soil condition and fertility. Digging is well developed especially in Australian mammals, many of which have recently become rare or extinct. We measured the effects of digging by mammals on soil in a Tasmanian temperate dry sclerophyll forest with an intact mammal community. The density of diggings was 5812 ha-1, affecting 11% of the forest floor. Diggings were created at a rate of around 3113 diggings ha-1 yr-1, disturbing 6.5% of the forest floor and displacing 7.1 m3 ha-1 of soil annually. Most diggings were made by eastern bettongs (Bettongia gaimardi) and short-beaked echidnas (Tachyglossus aculeatus). Many (approx. 30%) fresh diggings consisted of re-excavations of old diggings. Novel diggings displaced 5 m3 ha yr-1 of soil. Diggings acted as traps for organic matter and sites for the formation of new soil, which had higher fertility and moisture content and lower hardness than undisturbed topsoil. These effects on soil fertility and structure were strongest in habitats with dry and poor soil. Creation of fine-scaled heterogeneity by mammals, and amelioration of dry and infertile soil, is a valuable ecosystem service that could be restored by reintroduction of digging mammals to habitats from which they have declined or gone extinct.

Modeling underwater noise propagation from marine hydrokinetic power devices through a time-domain, velocity-pressure solution.

Marine hydrokinetic (MHK) devices generate electricity from the motion of tidal and ocean currents, as well as ocean waves, to provide an additional source of renewable energy available to the United States. These devices are a source of anthropogenic noise in the marine ecosystem and must meet regulatory guidelines that mandate a maximum amount of noise that may be generated. In the absence of measured levels from in situ deployments, a model for predicting the propagation of sound from an array of MHK sources in a real environment is essential. A set of coupled, linearized velocity-pressure equations in the time-domain are derived and presented in this paper, which are an alternative solution to the Helmholtz and wave equation methods traditionally employed. Discretizing these equations on a three-dimensional (3D), finite-difference grid ultimately permits a finite number of complex sources and spatially varying sound speeds, bathymetry, and bed composition. The solution to this system of equations has been parallelized in an acoustic-wave propagation package developed at Sandia National Labs, called Paracousti. This work presents the broadband sound pressure levels from a single source in two-dimensional (2D) ideal and Pekeris wave-guides and in a 3D domain with a sloping boundary. The paper concludes with demonstration of Paracousti for an array of MHK sources in a simple wave-guide.

What caused extinction of the Pleistocene megafauna of Sahul?

During the Pleistocene, Australia and New Guinea supported a rich assemblage of large vertebrates. Why these animals disappeared has been debated for more than a century and remains controversial. Previous synthetic reviews of this problem have typically focused heavily on particular types of evidence, such as the dating of extinction and human arrival, and have frequently ignored uncertainties and biases that can lead to misinterpretation of this evidence. Here, we review diverse evidence bearing on this issue and conclude that, although many knowledge gaps remain, multiple independent lines of evidence point to direct human impact as the most likely cause of extinction.

Suspension of oysters reduces the populations of Vibrio parahaemolyticus and Vibrio vulnificus.

UNLABELLED: Vibrio parahaemolyticus (Vp) and Vibrio vulnificus (Vv) are associated with the consumption of raw oysters and cause illnesses ranging from simple gastroenteritis to life-threatening septicaemia. These halophilic bacteria are frequently found in marine and estuarine systems, accumulating within the tissues of a number of aquatic organisms and passing on to humans after consumption, through contaminated water, or via open wounds. As benthic organisms capable of filtering 40 gallons of water per hour, sediment is an important source of potentially pathogenic vibrios in oysters destined for raw consumption. This research used off-bottom oyster culture to reduce vibrio concentrations in oysters. Colony hybridization was used to enumerate Vp and Vv in bottom and suspended oysters. Vv and Vp concentrations were generally lower in oysters suspended off-bottom, and suspension decreased vibrio loads in oysters by an average of 13%. Suspension of oysters reduced vibrio concentrations. SIGNIFICANCE AND IMPACT OF THE STUDY: This study found that oyster suspension significantly reduced some populations of potentially pathogenic vibrios. These results indicate that oyster suspension could be a viable approach for preharvest treatment to reduce illness in consumers of raw oysters.

Relationships between environmental factors and pathogenic Vibrios in the Northern Gulf of Mexico.

Although autochthonous vibrio densities are known to be influenced by water temperature and salinity, little is understood about other environmental factors associated with their abundance and distribution. Densities of culturable Vibrio vulnificus containing vvh (V. vulnificus hemolysin gene) and V. parahaemolyticus containing tlh (thermolabile hemolysin gene, ubiquitous in V. parahaemolyticus), tdh (thermostable direct hemolysin gene, V. parahaemolyticus pathogenicity factor), and trh (tdh-related hemolysin gene, V. parahaemolyticus pathogenicity factor) were measured in coastal waters of Mississippi and Alabama. Over a 19-month sampling period, vibrio densities in water, oysters, and sediment varied significantly with sea surface temperature (SST). On average, tdh-to-tlh ratios were significantly higher than trh-to-tlh ratios in water and oysters but not in sediment. Although tlh densities were lower than vvh densities in water and in oysters, the opposite was true in sediment. Regression analysis indicated that SST had a significant association with vvh and tlh densities in water and oysters, while salinity was significantly related to vibrio densities in the water column. Chlorophyll a levels in the water were correlated significantly with vvh in sediment and oysters and with pathogenic V. parahaemolyticus (tdh and trh) in the water column. Furthermore, turbidity was a significant predictor of V. parahaemolyticus density in all sample types (water, oyster, and sediment), and its role in predicting the risk of V. parahaemolyticus illness may be more important than previously realized. This study identified (i) culturable vibrios in winter sediment samples, (ii) niche-based differences in the abundance of vibrios, and (iii) predictive signatures resulting from correlations between environmental parameters and vibrio densities.

Distribution of type III secretion systems in Vibrio parahaemolyticus from the northern Gulf of Mexico.

AIMS: Two well-characterized Vibrio parahaemolyticus pathogenicity factors - thermostable direct haemolysin (TDH) and TDH-related haemolysin - are produced by strains containing the tdh and trh genes, respectively. Most strains of V. parahaemolyticus contain two nonredundant type III secretion systems (T3SS), T3SS1 and T3SS2, both of which contribute to pathogenicity. Furthermore, a recent study has revealed two distinct lineages of the V. parahaemolyticus T3SS2: T3SS2α and T3SS2ß. The aim of this study was to determine the incidence of these pathogenicity factors in environmental isolates of V. parahaemolyticus. METHODS AND RESULTS: We collected 130 V. parahaemolyticus isolates (TCBS agar) containing tdh and/or trh (determined by colony hybridization) from sediment, oyster and water in the northern Gulf of Mexico and screened them and 12 clinical isolates (PCR and agarose gel electrophoresis) for pathogenicity factors tdh, trh, T3SS1, T3SS2α and T3SS2ß. The majority of potential pathogens were detected in the sediment, including all tdh(-) /trh(+) isolates. T3SS2α components were detected in all tdh(+) /trh(-) isolates and zero of 109 trh(+) isolates. One T3SS2α gene, vopB2, was found in all tdh(+) /trh(-) clinical strains but not in any of the 130 environmental strains. Fluorescence in situ hybridization adapted for individual gene recognition (RING-FISH) was used to confirm the presence/absence of vopB2. T3SS2ß was found in all tdh(-) /trh(+) isolates and in no tdh(+) /trh(-) isolates. CONCLUSIONS: The combination of haemolysins found in each isolate consistently corresponded to the presence and type of T3SS detected. The vopB2 gene may represent a novel marker for identifying increased virulence among strains. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to confirm the presence of T3SS2ß genes in V. parahaemolyticus strains isolated from the Gulf of Mexico and one of the few that examines the distribution and co-existence of tdh, trh, T3SS1, T3SS2α and T3SS2ß in a large collection of environmental strains.

Ecological specialization and population size in a biodiversity hotspot: how rare species avoid extinction.

Species with narrow environmental niches typically have small geographic ranges. Small range size is, in turn, often associated with low local abundance. Together, these factors should mean that ecological specialists have very small total populations, putting them at high risk of extinction. But some specialized and geographically restricted species are ancient, and some ecological communities have high proportions of rare and specialized endemics. We studied niche characteristics and patterns of distribution and abundance of terrestrial vertebrates in the rainforests of the Australian Wet Tropics (AWT) to identify mechanisms by which rare species might resist extinction. We show that species with narrow environmental niches and small geographic ranges tend to have high and uniform local abundances. The compensation of geographic rarity by local abundance is exact, such that total population size in the rainforest vertebrates of the AWT is independent of environmental specialization. This effect would tend to help equalize extinction risk for specialists and generalists. Phylogenetic analysis suggests that environmental specialists have been gradually accumulating in this fauna, indicating that small range size/environmental specialization can be a successful trait as long as it is compensated for by demographic commonness. These results provide an explanation of how range-restricted specialists can persist for long periods, so that they now form a major component of high-diversity assemblages such as the AWT.

Ecological consequences of Late Quaternary extinctions of megafauna.

Large herbivorous vertebrates have strong interactions with vegetation, affecting the structure, composition and dynamics of plant communities in many ways. Living large herbivores are a small remnant of the assemblages of giants that existed in most terrestrial ecosystems 50,000 years ago. The extinction of so many large herbivores may well have triggered large changes in plant communities. In several parts of the world, palaeoecological studies suggest that extinct megafauna once maintained vegetation openness, and in wooded landscapes created mosaics of different structural types of vegetation with high habitat and species diversity. Following megafaunal extinction, these habitats reverted to more dense and uniform formations. Megafaunal extinction also led to changes in fire regimes and increased fire frequency due to accumulation of uncropped plant material, but there is a great deal of variation in post-extinction changes in fire. Plant communities that once interacted with extinct large herbivores still contain many species with obsolete defences against browsing and non-functional adaptations for seed dispersal. Such plants may be in decline, and, as a result, many plant communities may be in various stages of a process of relaxation from megafauna-conditioned to megafauna-naive states. Understanding the past role of giant herbivores provides fundamental insight into the history, dynamics and conservation of contemporary plant communities.

Genetic relatedness among tdh+ and trh+ Vibrio parahaemolyticus cultured from Gulf of Mexico oysters (Crassostrea virginica) and surrounding water and sediment.

Pathogenic Vibrio parahaemolyticus (Vp) (tdh(+)/trh(+)) represent a small percentage of environmental Vp populations, and very little is known about this subpopulation. Repetitive extragenic palindromic PCR and multilocus sequence analysis revealed heterogeneity among 41 Vp containing thermostable direct hemolysin (tdh) and tdh-related hemolysin (trh) that were isolated from Mississippi coastal environments from October 2006 to April 2007. There was no source-specific sequestering in oysters, water, or sediment.

Variability of total and pathogenic Vibrio parahaemolyticus densities in northern Gulf of Mexico water and oysters.

Vibrio parahaemolyticus is indigenous to coastal environments and a frequent cause of seafood-borne gastroenteritis in the United States, primarily due to raw-oyster consumption. Previous seasonal-cycle studies of V. parahaemolyticus have identified water temperature as the strongest environmental predictor. Salinity has also been identified, although it is evident that its effect on annual variation is not as pronounced. The effects of other environmental factors, both with respect to the seasonal cycle and intraseasonal variation, are uncertain. This study investigated intraseasonal variations of densities of total and pathogenic V. parahaemolyticus organisms in oysters and overlying waters during the summer of 2004 at two sites in the northern Gulf of Mexico. Regression analyses indicated significant associations (P < 0.001) between total V. parahaemolyticus densities and salinity, as well as turbidity in water and in oysters at the Mississippi site but not at the Alabama site. Pathogenic V. parahaemolyticus organisms in Mississippi oyster and water samples were detected in 56% (9 out of 16) and 78% (43 out of 55) of samples, respectively. In contrast, 44% (7 out of 16) of oyster samples and 30% (14 out of 47) of water samples from Alabama were positive. At both sites, there was greater sample-to-sample variability in pathogenic V. parahaemolyticus densities than in total V. parahaemolyticus densities. These data suggest that, although total V. parahaemolyticus densities may be very informative, there is greater uncertainty when total V. parahaemolyticus densities are used to predict the risk of infection by pathogenic V. parahaemolyticus than previously recognized.

Bryophyte dispersal by flying foxes: a novel discovery.

This research provides the first evidence of dispersal of bryophytes and associated microorganisms through ingestion by a highly mobile vertebrate vector, the spectacled flying fox (Pteropus conspicillatus). Bryophyte fragments were found in faeces collected at four P. conspicillatus' camps in the Wet Tropics bioregion, northeastern Australia. These fragments were viable when grown in culture; live invertebrates and other organisms were also present. Our study has significantly increased understanding of the role of flying foxes as dispersal vectors in tropical forests.

Adaptation of the WHO guideline for residual DNA in parenteral vaccines produced on continuous cell lines to a limit for oral vaccines.

Although there is a WHO guidance for a limit on residual DNA for parenterally administered vaccines produced on continuous cell lines, there is no corresponding guidance for oral vaccines. To help determine an oral limit, we performed a study of Vero cell DNA uptake in rats, in which the relative uptake and persistence of Vero cell DNA administered orally was compared to its uptake when delivered intramuscularly (IM). The results of this study allowed the generation of an empirically derived IM versus oral factor (10(6)) representing the relative inefficiency of DNA uptake by oral administration. This factor was then applied to the WHO recommended parenteral limit of 10 ng/dose to determine a corresponding upper limit on the level of residual Vero cell DNA for an oral vaccine of 10 mg. As a conservative approach, this empirically determined limit was reduced 100-fold to 100 microg. Thus, the results of this animal study, together with additional evidence in the literature, support a residual DNA safety limit of 100 microg per dose for an oral vaccine produced on a continuous cell line.

Vancomycin-resistant enterococci: 15 years and counting.

We review the history of vancomycin-resistant enterococci (VRE) and propose a causal model illustrating the roles of exposure to VRE reservoirs, patient characteristics, antimicrobial exposure, and prevalence of VRE in the progression from potential VRE reservoirs to active disease in hospitalized patients. Differences in VRE colonization and VRE infection are discussed with respect to hospital surveillance methodology and implications for interventions. We further document clonal transmission of VRE in a large, urban, teaching hospital and demonstrate VRE susceptibility to a wide array of antimicrobial agents. This model can guide the identification of mutable factors that are focal points for intervention.

Determinants of loss of mammal species during the Late Quaternary 'megafauna' extinctions: life history and ecology, but not body size.

Extinctions of megafauna species during the Late Quaternary dramatically reduced the global diversity of mammals. There is intense debate over the causes of these extinctions, especially regarding the extent to which humans were involved. Most previous analyses of this question have focused on chronologies of extinction and on the archaeological evidence for human-megafauna interaction. Here, I take an alternative approach: comparison of the biological traits of extinct species with those of survivors. I use this to demonstrate two general features of the selectivity of Late Quaternary mammal extinctions in Australia, Eurasia, the Americas and Madagascar. First, large size was not directly related to risk of extinction; rather, species with slow reproductive rates were at high risk regardless of their body size. This finding rejects the 'blitzkrieg' model of overkill, in which extinctions were completed during brief intervals of selective hunting of large-bodied prey. Second, species that survived despite having low reproductive rates typically occurred in closed habitats and many were arboreal or nocturnal. Such traits would have reduced their exposure to direct interaction with people. Therefore, although this analysis rejects blitzkrieg as a general scenario for the mammal megafauna extinctions, it is consistent with extinctions being due to interaction with human populations.

In vitro activity of ABT-773, telithromycin and eight other antimicrobials against erythromycin-resistant Streptococcus pneumoniae respiratory isolates of children.

The activity of the ketolide ABT-773 against 180 erythromycin-resistant Streptococcus pneumoniae obtained from children was compared with telithromycin, azithromycin, clarithromyin, roxithromycin, clindamycin, penicillin, levofloxacin and gatifloxacin. Ketolide MICs were all < or =1 mg/l, with ABT-773 being the most potent of all drugs tested. MIC(90)s for macrolides and azithromycin in mefE+ isolates were 16-32 compared with >128 mg/l for ermB+ isolates. ABT-773 and telithromycin MIC(90)s for mefE+ isolates were 0.125 and 0.5, compared with 0.032 and 0.016 mg/l for ermB+ isolates and 0.5 and 1 mg/l, respectively, for isolates containing both genes. Clindamycin was active against mefE+ but not ermB+ isolates. 155 isolates were resistant to penicillin. All fluoroquinolone MICs were < 1 mg/l. Further studies of ketolides for treatment of paediatric S. pneumoniae infections are warranted.

Adjustment of offspring sex ratios in relation to the availability of resources for philopatric offspring in the common brushtail possum.

The local-resource-competition hypothesis predicts that where philopatric offspring compete for resources with their mothers, offspring sex ratios will be biased in favour of the dispersing sex. This should produce variation in sex ratios between populations in relation to differences in the availability of resources for philopatric offspring. However, previous tests of local resource competition in mammals have used indirect measures of resource availability and have focused on sex-ratio variation between species or individuals rather than between local populations. Here, we show that the availability of den sites predicts the offspring sex ratio in populations of the common brushtail possum. Female possums defend access to dens, and daughters, but not sons, occupy dens within their mother's range. However, the abundances of possums in our study areas were determined principally by food availability. Consequently, in food-rich areas with a high population density, the per-capita availability of dens was low, and the cost of having a daughter should have been high. This cost was positively correlated with male bias in the sex ratio at birth. Low per capita availability of dens was correlated with male bias in the sex ratio at birth.

Synthesis of novel quinone boronic ester derivatives via a highly regioselective Cr-mediated benzannulation reaction and their application in Pd-catalyzed coupling processes.

This paper describes the synthesis and reactivity of a novel class of quinone boronic esters. These compounds are prepared utilizing a highly regioselective Dötz annulation of Fischer carbene complexes with alkynylboronates. All substrates studied to date provided a single regioisomeric arylboronic ester product; the origin of this selectivity is discussed in the context of steric and electronic effects. Additionally, these compounds have been found to undergo Pd-catalyzed coupling reactions with a range of aryl and allyl halides and provides a strategy for the selective and predictable preparation of highly substituted quinones and hydroquinones. Finally, the propensity of this technique to prepare highly functionalized aromatic compounds in an expeditious fashion is demonstrated in the total synthesis of dimeric carbazole (+/-)-bis-N-dimethylbismurrayaquinone-A 33.

Design and synthesis of novel 2,3-dihydro-1H-isoindoles with high affinity and selectivity for the dopamine D3 receptor.

Starting from the tetrahydroisoquinoline SB-277011 1, a novel series of 5-substituted-2,3-dihydro-1H-isoindoles has been designed. Subsequent optimisation resulted in identification of 19, which has high affinity for the dopamine D3 receptor (pKi 8.3) and > or = 100-fold selectivity over other aminergic receptors. In rat studies 19 was brain penetrant with an excellent pharmacokinetic profile (oral bioavailability 77%, t1/2 5.2h).