Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 78
Filter
1.
Sci Rep ; 12(1): 16520, 2022 10 03.
Article in English | MEDLINE | ID: mdl-36192476

ABSTRACT

Effective mitigation of the impacts of invasive ship rats (Rattus rattus) requires a good understanding of their ecology, but this knowledge is very sparse for urban and peri-urban areas. We radiomarked ship rats in Wellington, New Zealand, to estimate detection parameters (σ, ε0, θ, and g0) that describe the process of an animal encountering a device (bait stations, chew cards and WaxTags) from a distance, and then approaching it and deciding whether to interact with it. We used this information in simulation models to estimate optimal device spacing for eradicating ship rats from Wellington, and for confirming eradication. Mean σ was 25.37 m (SD = 11.63), which equates to a circular home range of 1.21 ha. The mean nightly probability of an individual encountering a device at its home range center (ε0) was 0.38 (SD = 0.11), whereas the probability of interacting with the encountered device (θ) was 0.34 (SD = 0.12). The derived mean nightly probability of an individual interacting with a device at its home range center (g0) was 0.13 (SD = 0.08). Importantly, σ and g0 are intrinsically linked through a negative relationship, thus g0 should be derived from σ using a predictive model including individual variability. Simulations using this approach showed that bait stations deployed for about 500 days using a 25 m × 25 m grid consistently achieved eradication, and that a surveillance network of 3.25 chew cards ha-1 or 3.75 WaxTags ha-1 active for 14 nights would be required to confidently declare eradication. This density could be halved if the surveillance network was deployed for 28 nights or if the prior confidence in eradication was high (0.85). These recommendations take no account of differences in detection parameters between habitats. Therefore, if surveillance suggests that individuals are not encountering devices in certain habitats, device density should be adaptively revised. This approach applies to initiatives globally that aim to optimise eradication with limited funding.


Subject(s)
Introduced Species , Animals , New Zealand/epidemiology , Population Density , Rats
2.
Glob Ecol Biogeogr ; 31(8): 1526-1541, 2022 Aug.
Article in English | MEDLINE | ID: mdl-36247232

ABSTRACT

Aim: Macroecological studies that require habitat suitability data for many species often derive this information from expert opinion. However, expert-based information is inherently subjective and thus prone to errors. The increasing availability of GPS tracking data offers opportunities to evaluate and supplement expert-based information with detailed empirical evidence. Here, we compared expert-based habitat suitability information from the International Union for Conservation of Nature (IUCN) with habitat suitability information derived from GPS-tracking data of 1,498 individuals from 49 mammal species. Location: Worldwide. Time period: 1998-2021. Major taxa studied: Forty-nine terrestrial mammal species. Methods: Using GPS data, we estimated two measures of habitat suitability for each individual animal: proportional habitat use (proportion of GPS locations within a habitat type), and selection ratio (habitat use relative to its availability). For each individual we then evaluated whether the GPS-based habitat suitability measures were in agreement with the IUCN data. To that end, we calculated the probability that the ranking of empirical habitat suitability measures was in agreement with IUCN's classification into suitable, marginal and unsuitable habitat types. Results: IUCN habitat suitability data were in accordance with the GPS data (> 95% probability of agreement) for 33 out of 49 species based on proportional habitat use estimates and for 25 out of 49 species based on selection ratios. In addition, 37 and 34 species had a > 50% probability of agreement based on proportional habitat use and selection ratios, respectively. Main conclusions: We show how GPS-tracking data can be used to evaluate IUCN habitat suitability data. Our findings indicate that for the majority of species included in this study, it is appropriate to use IUCN habitat suitability data in macroecological studies. Furthermore, we show that GPS-tracking data can be used to identify and prioritize species and habitat types for re-evaluation of IUCN habitat suitability data.

3.
J Acquir Immune Defic Syndr ; 89(4): 448-453, 2022 04 01.
Article in English | MEDLINE | ID: mdl-35202051

ABSTRACT

BACKGROUND: We sought to determine whether pregnant women with HIV prescribed integrase strand transfer inhibitor (INSTI) were more likely to have viral suppression at delivery and any increased risk of adverse infant outcomes. METHODS: This was a retrospective, statewide cohort study of women with HIV and their HIV-exposed infants who delivered in South Carolina from 2008 to 2019. Women's antenatal AVRs were classified as INSTI or non-INSTI. We compared the percentage of women with undetectable HIV RNA viral load (<40 copies/mL) at delivery between groups. We compared the percentage of HIV-exposed singleton infants who were born preterm delivery, low birth weight, and small for gestational age and had confirmed perinatal HIV infection. Categorical outcomes were compared using the χ2 test or Fischer exact test. RESULTS: A total of 832 infants, including 11 sets of twins, were exposed to maternal HIV. Detailed antiretroviral regimens were available for analysis in a third of mother-infant pairs (n = 315). Half of the infants were exposed to INSTI (159) and half to non-INSTI antiretrovirals (156). Most women had an undetectable viral load at delivery (80% INSTI and 73% non-INSTI, P= 0.11). The percentage of singleton infants with adverse outcomes was similar between INSTI and non-INSTI groups: preterm delivery (21% and 16%, P = 0.3), low birth weight (19% and 21%, P = 0.7), small for gestational age (11% vs 9%, P = 0.5), and perinatal HIV infection (2.5% and 1.3%, P = 0.7). CONCLUSIONS: We observed that viral suppression before delivery was similar between pregnant women prescribed INSTI and non-INSTI antiretroviral therapy. The percentage of infants with adverse outcomes was similar when exposed to INSTI and non-INSTI antiretroviral therapy.


Subject(s)
HIV Infections , HIV Integrase Inhibitors , Cohort Studies , Female , HIV Infections/drug therapy , HIV Integrase Inhibitors/therapeutic use , Humans , Infant , Infant, Newborn , Integrases , Pregnancy , Retrospective Studies , Viral Load
4.
Sci Adv ; 7(11)2021 03.
Article in English | MEDLINE | ID: mdl-33692107

ABSTRACT

Efficient decision-making integrates previous experience with new information. Tactical use of misinformation can alter choice in humans. Whether misinformation affects decision-making in other free-living species, including problem species, is unknown. Here, we show that sensory misinformation tactics can reduce the impacts of predators on vulnerable bird populations as effectively as lethal control. We repeatedly exposed invasive mammalian predators to unprofitable bird odors for 5 weeks before native shorebirds arrived for nesting and for 8 weeks thereafter. Chick production increased 1.7-fold at odor-treated sites over 25 to 35 days, with doubled or tripled odds of successful hatching, resulting in a 127% increase in modeled population size in 25 years. We demonstrate that decision-making processes that respond to changes in information reliability are vulnerable to tactical manipulation by misinformation. Altering perceptions of prey availability offers an innovative, nonlethal approach to managing problem predators and improving conservation outcomes for threatened species.

5.
Ecol Appl ; 30(8): e02200, 2020 12.
Article in English | MEDLINE | ID: mdl-32573866

ABSTRACT

Invasive mammalian predators can cause the decline and extinction of vulnerable native species. Many invasive mammalian predators are dietary generalists that hunt a variety of prey. These predators often rely upon olfaction when foraging, particularly at night. Little is understood about how prey odor cues are used to inform foraging decisions. Prey cues can vary spatially and temporally in their association with prey and can either reveal the location of prey or lead to unsuccessful foraging. Here we examine how two wild-caught invasive mammalian bird predator species (European hedgehogs Erinaceus europaeus and ferrets Mustela putorius furo) respond to unrewarded bird odors over successive exposures, first demonstrating that the odors are perceptually different using house mice (Mus musculus) as a biological olfactometer. We aim to test if introduced predators categorize odor cues of similar prey together, a tactic that could increase foraging efficiency. We exposed house mice to the odors using a standard habituation/dishabituation test in a laboratory setting, and wild-caught European hedgehogs and ferrets in an outdoor enclosure using a similar procedure. Mice discriminated among all bird odors presented, showing more interest in chicken odor than quail or gull odor. Both predator species showed a decline in interest toward unrewarded prey odor (i.e., habituation), but only ferrets generalized their response from one unrewarded bird odor to another bird odor. Hedgehog responses to unrewarded bird odors were highly variable between individuals. Taken together, our results reveal interspecific and intraspecific differences in response to prey odors, which we argue are a consequence of different diet breadth, life and evolutionary histories, and the conditions in each experiment. Generalization of prey odors may have enabled some species of invasive predators to efficiently hunt a range of intraguild prey species, for example, ground-nesting shorebirds. Olfactory manipulation of predators may be a useful conservation tool for threatened prey if it reduces the conspicuousness of vulnerable prey.


Subject(s)
Cues , Predatory Behavior , Animals , Birds , Mammals , Mice , Odorants
6.
Animals (Basel) ; 10(1)2019 Dec 24.
Article in English | MEDLINE | ID: mdl-31878314

ABSTRACT

All capture methods impose animal welfare impacts, but these impacts are rarely quantified or reported. We present data from two wildlife capture studies that trialled new methods for capturing Bennett's wallabies (Notamacropus rufogriseus) and red deer (Cervus elaphus) in New Zealand. We used helicopter net-gunning for both species, and compared this method with ground-based netting for wallabies and helicopter darting for red deer, using, for the first time in New Zealand, the fast-acting opioid thiafentanil. Efficacy and animal welfare parameters quantified were duration of handling and recovery, and frequency of adverse events, including escape, injury, and mortality. Cost-effectiveness was quantified for each method. Capture mortalities occurred for all methods for both species. For red deer, chemical immobilisation led to fewer traumatic injuries and fewer mortalities, while for wallabies, net-gunning led to fewer mortalities. Net-gunning was an efficient capture method for deer in open habitat, but led to the escape of 54% of wallabies and one wallaby mortality (4%). Ground-based netting resulted in the mortality of 17% of wallabies at the time of capture, and the capture of non-target species. The cost per captured wallaby was 40% more expensive for net-gunning (NZ$1045) than for ground-based netting (NZ$745), but, once corrected for mortalities at the time of capture and suitability of individuals for GPS-collar deployment, this was reduced to 29% and 12% more expensive, respectively. Net-gunning for red deer resulted in the escape of 13% of animals and mortality of 10% of animals at the time of capture. Helicopter-based darting for red deer using thiafentanil (c. 0.03-0.06 mg/kg) had high capture efficacy (zero escapes), rapid induction times (mean of 3 min), and a low mortality rate at 14 days post-capture (3%), but it was more expensive per deer captured and collared than aerial netting (NZ$2677 and NZ$2234, respectively). We recommend reporting of adverse event data for all wildlife capture techniques to permit continual refinement of field methods.

7.
Ecol Appl ; 29(1): e01814, 2019 01.
Article in English | MEDLINE | ID: mdl-30312506

ABSTRACT

Foraging mammalian predators face a myriad of odors from potential prey. To be efficient, they must focus on rewarding odors while ignoring consistently unrewarding ones. This may be exploited as a nonlethal conservation tool if predators can be deceived into ignoring odors of vulnerable secondary prey. To explore critical design components and assess the potential gains to prey survival of this technique, we created an individual-based model that simulated the hunting behavior of three introduced mammalian predators on one of their secondary prey (a migratory shorebird) in the South Island of New Zealand. Within this model, we heuristically assessed the outcome of habituating the predators to human-deployed unrewarding bird odors before the bird's arrival at their breeding grounds, i.e., the predators were "primed." Using known home range sizes and probabilities of predators interacting with food lures, our model suggests that wide-ranging predators should encounter a relatively large number of odor points (between 10 and 115) during 27 d of priming when odor is deployed within high-resolution grids (100-150 m). Using this information, we then modeled the effect of different habituation curves (exponential and sigmoidal) on the probability of predators depredating shorebird nests. Our results show that important gains in nest survival can be achieved regardless of the shape of the habituation curve, but particularly if predators are fast olfactory learners (exponential curve), and even if some level of dishabituation occurs after prey become available. Predictions from our model can inform the amount and pattern in which olfactory stimuli need to be deployed in the field to optimize encounters by predators, and the relative gains that can be expected from reduced predation pressure on secondary prey under different scenarios of predator learning. Habituating predators to odors of threatened secondary prey may have particular efficacy as a conservation tool in areas where lethal predator control is not possible or ethical, or where even low predator densities can be detrimental to prey survival. Our approach is also relevant for determining interaction probabilities for devices other than odor points, such as bait stations and camera traps.


Subject(s)
Birds , Odorants , Animals , Humans , Mammals , New Zealand , Predatory Behavior
8.
Clin Pharmacol Ther ; 101(4): 519-530, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27943276

ABSTRACT

A microdose cocktail containing midazolam, dabigatran etexilate, pitavastatin, rosuvastatin, and atorvastatin has been established to allow simultaneous assessment of a perpetrator impact on the most common drug metabolizing enzyme, cytochrome P450 (CYP)3A, and the major transporters organic anion-transporting polypeptides (OATP)1B, breast cancer resistance protein (BCRP), and MDR1 P-glycoprotein (P-gp). The clinical utility of these microdose cocktail probe substrates was qualified by conducting clinical drug interaction studies with three inhibitors with different in vitro inhibitory profiles (rifampin, itraconazole, and clarithromycin). Generally, the pharmacokinetic profiles of the probe substrates, in the absence and presence of the inhibitors, were comparable to their reported corresponding pharmacological doses, and/or in agreement with theoretical expectations. The exception was dabigatran, which resulted in an approximately twofold higher magnitude for microdose compared to conventional dosing, and, thus, can be used to flag a worst-case scenario for P-gp. Broader application of the microdose cocktail will facilitate a more comprehensive understanding of the roles of drug transporters in drug disposition and drug interactions.


Subject(s)
Carrier Proteins/metabolism , Cytochrome P-450 CYP3A/metabolism , Drug Combinations , Drug Interactions , ATP Binding Cassette Transporter, Subfamily B/metabolism , ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism , Adult , Area Under Curve , Carrier Proteins/antagonists & inhibitors , Cell Line , Cytochrome P-450 CYP3A Inhibitors/adverse effects , Cytochrome P-450 CYP3A Inhibitors/therapeutic use , Drug-Related Side Effects and Adverse Reactions/enzymology , Drug-Related Side Effects and Adverse Reactions/metabolism , Female , Healthy Volunteers , Humans , Liver-Specific Organic Anion Transporter 1/metabolism , Male , Middle Aged , Neoplasm Proteins/metabolism , Pharmacokinetics , Tissue Distribution , Young Adult
9.
PLoS One ; 11(6): e0158078, 2016.
Article in English | MEDLINE | ID: mdl-27341209

ABSTRACT

European rabbits (Oryctolagus cuniculus) pose a major threat to agricultural production and conservation values in several countries. In New Zealand, population control via poisoning is a frontline method for limiting rabbit damage, with large areas commonly treated using the metabolic toxin sodium fluoroacetate ('1080') delivered in bait via aerial dispersal. However, this method is expensive and the high application rates of the active ingredient cause public antipathy towards it. To guide reductions in cost and toxin usage, we evaluated the economics and efficacy of rabbit control using an experimental approach of sowing 1080-bait in strips instead of the commonly-used broadcast sowing method (i.e. complete coverage). Over a 4-year period we studied aerial delivery of 0.02% 1080 on diced carrot bait over ~3500 ha of rabbit-prone land in the North and South islands. In each case, experimental sowing via strip patterns using 10-15 kg of bait per hectare was compared with the current best practice of aerial broadcast sowing at 30-35 kg/ha. Operational kill rates exceeded 87% in all but one case and averaged 93-94% across a total of 19 treatment replicates under comparable conditions; there was no statistical difference in overall efficacy observed between the two sowing methods. We project that strip-sowing could reduce by two thirds the amount of active 1080 applied per hectare in aerial control operations against rabbits, both reducing the non-target poisoning risk and promoting cost savings to farming operations. These results indicate that, similarly to the recently-highlighted benefits of adopting strip-sowing for poison control of introduced brushtail possums (Trichosurus vulpecula) in New Zealand, aerial strip-sowing of toxic bait could also be considered a best practice method for rabbit control in pest control policy.


Subject(s)
Agriculture , Introduced Species , Pest Control , Population Control , Animals , Cost-Benefit Analysis , Geography , New Zealand , Rabbits
10.
J Biol Dyn ; 9: 229-46, 2015.
Article in English | MEDLINE | ID: mdl-26192082

ABSTRACT

We study an epidemic model that incorporates risk-taking behaviour as a response to a perceived low prevalence of infection that follows from the administration of an effective treatment or vaccine. We assume that knowledge about the number of infected, recovered and vaccinated individuals has an effect in the contact rate between susceptible and infectious individuals. We show that, whenever optimism prevails in the risk behaviour response, the fate of an epidemic may change from disease clearance to disease persistence. Moreover, under certain conditions on the parameters, increasing the efficiency of vaccine and/or treatment has the unwanted effect of increasing the epidemic reproductive number, suggesting a wider range of diseases may become endemic due to risk-taking alone. These results indicate that the manner in which treatment/vaccine effectiveness is advertised can have an important influence on how the epidemic unfolds.


Subject(s)
Epidemics , Risk-Taking , Basic Reproduction Number , Humans , Influenza, Human/epidemiology , Influenza, Human/transmission , Models, Biological , Prevalence , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/transmission , Vaccination
11.
Vet Res ; 45: 122, 2014 Dec 12.
Article in English | MEDLINE | ID: mdl-25496754

ABSTRACT

Controlling infectious diseases at the wildlife/livestock interface is often difficult because the ecological processes driving transmission between wildlife reservoirs and sympatric livestock populations are poorly understood. Thus, assessing how animals use their environment and how this affects interspecific interactions is an important factor in determining the local risk for disease transmission and maintenance. We used data from concurrently monitored GPS-collared domestic cattle and wild boar (Sus scrofa) to assess spatiotemporal interactions and associated implications for bovine tuberculosis (TB) transmission in a complex ecological and epidemiological system, Doñana National Park (DNP, South Spain). We found that fine-scale spatial overlap of cattle and wild boar was seasonally high in some habitats. In general, spatial interactions between the two species were highest in the marsh-shrub ecotone and at permanent water sources, whereas shrub-woodlands and seasonal grass-marshlands were areas with lower predicted relative interactions. Wild boar and cattle generally used different resources during winter and spring in DNP. Conversely, limited differences in resource selection during summer and autumn, when food and water availability were limiting, resulted in negligible spatial segregation and thus probably high encounter rates. The spatial gradient in potential overlap between the two species across DNP corresponded well with the spatial variation in the observed incidence of TB in cattle and prevalence of TB in wild boar. We suggest that the marsh-shrub ecotone and permanent water sources act as important points of TB transmission in our system, particularly during summer and autumn. Targeted management actions are suggested to reduce potential interactions between cattle and wild boar in order to prevent disease transmission and design effective control strategies.


Subject(s)
Animal Distribution , Cattle Diseases/transmission , Feeding Behavior , Swine Diseases/transmission , Tuberculosis, Bovine/transmission , Animals , Cattle/physiology , Cattle Diseases/epidemiology , Cattle Diseases/microbiology , Female , Geographic Information Systems , Incidence , Male , Prevalence , Spain/epidemiology , Swine/physiology , Swine Diseases/epidemiology , Swine Diseases/microbiology , Tuberculosis, Bovine/epidemiology , Tuberculosis, Bovine/microbiology
12.
PLoS One ; 9(7): e102982, 2014.
Article in English | MEDLINE | ID: mdl-25054199

ABSTRACT

Estimating the abundance of wild carnivores is of foremost importance for conservation and management. However, given their elusive habits, direct observations of these animals are difficult to obtain, so abundance is more commonly estimated from sign surveys or radio-marked individuals. These methods can be costly and difficult, particularly in large areas with heavy forest cover. As an alternative, recent research has suggested that wolf abundance can be estimated from occupancy-abundance curves derived from "virtual" surveys of simulated wolf track networks. Although potentially more cost-effective, the utility of this approach hinges on its robustness to violations of its assumptions. We assessed the sensitivity of the occupancy-abundance approach to four assumptions: variation in wolf movement rates, changes in pack cohesion, presence of lone wolves, and size of survey units. Our simulations showed that occupancy rates and wolf pack abundances were biased high if track surveys were conducted when wolves made long compared to short movements, wolf packs were moving as multiple hunting units as opposed to a cohesive pack, and lone wolves were moving throughout the surveyed landscape. We also found that larger survey units (400 and 576 km2) were more robust to changes in these factors than smaller survey units (36 and 144 km2). However, occupancy rates derived from large survey units rapidly reached an asymptote at 100% occupancy, suggesting that these large units are inappropriate for areas with moderate to high wolf densities (>15 wolves/1,000 km2). Virtually-derived occupancy-abundance relationships can be a useful method for monitoring wolves and other elusive wildlife if applied within certain constraints, in particular biological knowledge of the surveyed species needs to be incorporated into the design of the occupancy surveys. Further, we suggest that the applicability of this method could be extended by directly incorporating some of its assumptions into the modelling framework.


Subject(s)
Ecosystem , Models, Theoretical , Wolves , Alberta , Animals , Conservation of Natural Resources , Population Dynamics
13.
Br J Pharmacol ; 165(1): 245-59, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21699503

ABSTRACT

BACKGROUND AND PURPOSE: The potent pro-angiogenic growth factors VEGF-A and basic fibroblast growth factor (bFGF) exert their effects by binding VEGF receptor 2 and FGF receptor tyrosine kinases, respectively. Indolinones (e.g. SU5416 and Sutent) and anilinophthalazines (e.g. PTK787) are potent small molecule inhibitors of VEGFR2 and other tyrosine kinases, but their effects on VEGF-A- and bFGF-stimulated endothelial responses are unclear. Here we assess the ability of these compounds to inhibit pro-angiogenic responses through perturbation of receptor activity and endothelial function(s). EXPERIMENTAL APPROACH: We used in silico modelling, in vitro tyrosine kinase assays, biochemistry and microscopy to evaluate the effects of small molecules on receptor tyrosine kinase activation and intracellular signalling. Primary human endothelial cells were used to assess intracellular signalling, cell migration, proliferation and tubulogenesis. KEY RESULTS: We predicted that the anilinophthalazine PTK787 binds the tyrosine kinase activation loop whereas indolinones are predicted to bind within the hinge region of the split kinase domain. Sutent is a potent inhibitor of both VEGFR2 and FGFR1 tyrosine kinase activity in vitro. The compounds inhibit both ligand-dependent and -independent VEGFR2 trafficking events, are not selective for endothelial cell responses and inhibit both VEGF-A- and bFGF-mediated migration, wound healing and tubulogenesis at low concentrations. CONCLUSIONS AND IMPLICATIONS; We propose that these compounds have novel properties including inhibition of bFGF-mediated endothelial responses and perturbation of VEGFR2 trafficking. Differential inhibitor binding to receptor tyrosine kinases translates into more potent inhibition of bFGF- and VEGF-A-mediated intracellular signalling, cell migration and tubulogenesis. Indolinones and anilinophthalazines thus belong to a class of multi-kinase inhibitors that show clinical efficacy in disease therapy.


Subject(s)
Endothelial Cells/drug effects , Fibroblast Growth Factor 2/metabolism , Indoles/pharmacology , Phthalazines/pharmacology , Vascular Endothelial Growth Factor A/metabolism , Adenosine Triphosphate/metabolism , Catalytic Domain , Computer Simulation , Endothelial Cells/metabolism , Fibroblast Growth Factor 2/genetics , Gene Expression Profiling , Gene Expression Regulation/drug effects , Humans , Models, Biological , Models, Molecular , Protein Binding , Protein Conformation , Receptor, Fibroblast Growth Factor, Type 1/genetics , Receptor, Fibroblast Growth Factor, Type 1/metabolism , Signal Transduction , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor Receptor-2/genetics , Vascular Endothelial Growth Factor Receptor-2/metabolism
14.
Br J Pharmacol ; 166(2): 737-48, 2012 May.
Article in English | MEDLINE | ID: mdl-22141913

ABSTRACT

BACKGROUND AND PURPOSE: Vascular endothelial growth factor receptor 2 (VEGFR2) is an attractive therapeutic target for the treatment of diseases such as cancer. Small-molecule VEGFR2 inhibitors of a variety of chemical classes are currently under development or in clinical use. In this study, we describe the de novo design of a new generation pyrazole-based molecule (JK-P3) that targets VEGFR2 kinase activity and angiogenesis. EXPERIMENTAL APPROACH: JK-P compound series were designed using de novo structure-based identification methods. Compounds were tested in an in vitro VEGFR2 kinase assay. Using primary endothelial cells, JK-P compounds were assessed for their ability to inhibit VEGF-A-stimulated VEGFR2 activation and intracellular signalling. We tested these compounds in cell migration, proliferation and angiogenesis assays. KEY RESULTS: JK-P3 and JK-P5 were predicted to bind the VEGFR2 kinase domain with high affinity, and both compounds showed pronounced inhibition of endogenous VEGFR2 kinase activity in primary human endothelial cells. Only JK-P3 inhibited VEGF-A-stimulated VEGFR2 activation and intracellular signalling. Interestingly, JK-P3 inhibited endothelial monolayer wound closure and angiogenesis but not endothelial cell proliferation. Both compounds inhibited fibroblast growth factor receptor kinase activity in vitro, but not basic fibroblast growth factor-mediated signalling in endothelial cells. CONCLUSIONS AND IMPLICATIONS: This is the first report that describes an anti-angiogenic inhibitor based on such a pyrazole core. Using a de novo structure-based identification approach is an attractive method to aid such drug discovery. These results thus provide an important basis for the development of multi-tyrosine kinase inhibitors for clinical use in the near future.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Neovascularization, Physiologic/physiology , Protein Kinase Inhibitors/pharmacology , Pyrazoles/pharmacology , Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors , Cell Proliferation/drug effects , Computer-Aided Design , Drug Design , Human Umbilical Vein Endothelial Cells , Humans , Receptor, Fibroblast Growth Factor, Type 1/antagonists & inhibitors , Receptor, Fibroblast Growth Factor, Type 1/metabolism , Receptor, Fibroblast Growth Factor, Type 3/antagonists & inhibitors , Receptor, Fibroblast Growth Factor, Type 3/metabolism , Vascular Endothelial Growth Factor A/pharmacology , Vascular Endothelial Growth Factor Receptor-2/metabolism , Wound Healing/drug effects
15.
J Hum Evol ; 52(4): 388-400, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17196239

ABSTRACT

The sediments in the western side of the Makapansgat Limeworks were either precipitated as speleothems, represented in the earlier massive deposits, or were deposited as coarsening clastic sediments, mainly representing later deposits. Between the earlier deposits and the main sedimentary phase, the stratigraphic sequence was inverted twice to a considerable height by the unusual deposition of subaqueous speleothem. Bone-bearing deposits, including the Main Quarry Bone Breccia and the well-known Grey Breccia belong, in time, to the lower part of the clastic deposits called the Red Silts. Australopith fossils have been found in the Grey Breccia dumped material and, in situ, from the dolomite clast breccia on the Main Quarry entrance buttress. Whatever the problems may be in provenancing some of the material from the Limeworks dumps, there is no doubt that the three rows of blocks on the southern side of the dumps belong to the Grey Breccia, and other rows contain red sediment sufficient for them to be safely associated with the Red Silts. There is no reason why this material should not be prepared with confidence as to its stratigraphic provenance. In any case, stratigraphic evidence, presented here, shows that there is little difference in time between the deposition of the bone-bearing breccias.


Subject(s)
Fossils , Geologic Sediments , Animals , Bone and Bones , South Africa
16.
Phys Rev Lett ; 96(11): 111301, 2006 Mar 24.
Article in English | MEDLINE | ID: mdl-16605810

ABSTRACT

We reconsider the predictions of inflation for the spectral index of scalar (energy density) fluctuations (ns) and the tensor/scalar ratio (r) using a discrete, model-independent measure of the degree of fine-tuning required to obtain a given combination of (ns, r ). We find that, except for cases with numerous unnecessary degrees of fine-tuning, ns is less than 0.98, measurably different from exact Harrison-Zel'dovich. Furthermore, if ns >or= 0.95, in accord with current measurements, the tensor/scalar ratio satisfies r >or= 10(-2), a range that should be detectable in proposed cosmic microwave background polarization experiments and direct gravitational wave searches.

17.
Folia Parasitol (Praha) ; 50(2): 109-14, 2003 Jun.
Article in English | MEDLINE | ID: mdl-14560971

ABSTRACT

Previously undescribed third-stage larvae of two species of Spirurida were found in the haemocoel of the stalk-eyed mud crab Macrophthalmus hirtipes (Heller) (Ocypodidae) in New Zealand. Examinations by light and scanning electron microscopy showed that the larger larvae (about 7 mm long) belonged to a species of Ascarophis van Beneden, 1871 (Cystidicolidae), the genus including parasites of fishes, whereas the smaller larvae (about 4-5 mm long) belonged to the Acuariidae, a family with species parasitic as adults mostly in aquatic birds. In a sample of 82 specimens of M. hirtipes collected in July 2002 from Papanui Inlet, on Otago Peninsula, South Island, 74 crabs (90.2%) were infected with larval nematodes with an intensity of 1-18 (mean 4.6) nematodes per crab; no distinction between nematode species was made in these estimates, although juvenile Acuariidae greatly outnumbered larval Ascarophis. Apparently, crabs play a role as intermediate hosts of these nematode species. This is the first record of larval representatives of Cystidicolidae and Acuariidae from invertebrates in the Australasian Region.


Subject(s)
Brachyura/parasitology , Spirurida/classification , Spirurida/isolation & purification , Animals , Larva/ultrastructure , Microscopy, Electron, Scanning , New Zealand , Spirurida/growth & development , Spirurida/ultrastructure
18.
J Parasitol ; 89(4): 862-4, 2003 Aug.
Article in English | MEDLINE | ID: mdl-14533707

ABSTRACT

The whelk Cominella glandiformis is an important predator-scavenger of New Zealand intertidal ecosystems; a few whelks can quickly eat all the soft tissues of recently dead crabs. In this study, we demonstrate that whelks can also ingest and act as paratenic hosts for at least 4 helminth species that use crabs as intermediate hosts: metacercariae of the trematode Maritrema sp. and of another unidentified trematode, larval acuariid nematodes, and cystacanths of the acanthocephalans Profilicollis spp. Large whelks ingest disproportionately more helminth larvae than small whelks, but the survival of parasites during their short stay in the whelks is not affected by whelk size. The majority of metacercariae and nematodes are passed out in whelk feces within 3 days of ingestion, whereas the few cystacanths found did not leave whelks until after that time; no parasite was left in whelks 5 days postingestion. Survival of all 4 helminth species was generally very high, though it decreased day by day in 2 species. Given that the avian definitive hosts of all 4 helminths also eat whelks, our results indicate that alternative transmission pathways exist and that parasites can take routes through food webs that are too often ignored.


Subject(s)
Brachyura/parasitology , Helminths/isolation & purification , Mollusca/parasitology , Acanthocephala/isolation & purification , Animals , Nematoda/isolation & purification , Trematoda/isolation & purification
19.
Int J Parasitol ; 33(4): 425-33, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12705935

ABSTRACT

Larval helminths of different species that share the same intermediate host and are transmitted by predation to the same definitive host may cooperate in their attempts to manipulate the behaviour of the intermediate host, while at the same time having conflicts of interests over the use of host resources. A few studies have indicated that intermediate hosts harbouring larval helminths have altered concentrations of neurotransmitters in their nervous system, and thus measuring levels of neurotransmitters in host brains could serve to assess the respective and combined effect of different helminth species on host behaviour. Here, we investigate potential cooperation and conflict among three helminths in two species of crab intermediate hosts. The acanthocephalan Profilicollis spp., the trematode Maritrema sp. and an acuariid nematode, all use Macrophthalmus hirtipes (Ocypodidae) as intermediate host, whereas Profilicollis and Maritrema also use Hemigrapsus crenulatus (Grapsidae). All three helminths mature inside gulls or other shore birds. There was a significant decrease in the mean volume of Profilicollis cystacanths as the intensity of infection by this parasite increased in H. crenulatus, the only host in which this was investigated; however, there was no measurable effect of other helminth species on the size of acanthocephalans, suggesting no interspecific conflict over resource use within crabs. There was, in contrast, evidence of a positive interspecific association between the two most common helminth species: numbers of Profilicollis and Maritrema were positively correlated among crabs, independently of crab size, in M. hirtipes but not H. crenulatus. More importantly, we found that the total number of larval helminths per crab correlated significantly, and negatively, with concentrations of serotonin in crab brains, again only in M. hirtipes; numbers of each parasite species separately did not covary in either crab species with serotonin or dopamine, the other neurotransmitter investigated in this study. The relationship with serotonin appears due mainly to numbers of Profilicollis and Maritrema and not to nematodes. This is the first demonstration of a potentially synergistic manipulation of host behaviour by different helminth species, one that appears host-specific; our results also point toward the neurobiological mechanism underlying this phenomenon.


Subject(s)
Brachyura/parasitology , Helminths/physiology , Acanthocephala/physiology , Animals , Helminthiasis, Animal/parasitology , Host-Parasite Interactions
20.
J Helminthol ; 76(4): 323-6, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12498637

ABSTRACT

The effect of acanthocephalan parasites (Profilicollis spp.) on the hiding behaviour during low tide of two species of shore crabs (intermediate hosts), Macrophthalmus hirtipes (Brachyura: Ocypodidae) and Hemigrapsus crenulatus (Brachyura: Grapsidae), was examined at Blueskin Bay, South Island, New Zealand. Exposed M. hirtipes were found to have significantly higher infection levels than did hidden conspecifics. This pattern was not observed for H. crenulatus. Mean cystacanth numbers were found to be considerably higher in M. hirtipes than H. crenulatus. Crabs exposed at low tide are at a greater risk of predation by definitive shorebird hosts than are hidden conspecifics. Preferential manipulation of one intermediate host species over another could influence diversity within ecosystems.


Subject(s)
Acanthocephala/isolation & purification , Behavior, Animal , Brachyura/parasitology , Helminthiasis, Animal/parasitology , Acanthocephala/physiology , Animals , Female , Helminthiasis, Animal/psychology , Host-Parasite Interactions , Male , Predatory Behavior
SELECTION OF CITATIONS
SEARCH DETAIL
...