Prey identity but not prey quality affects spider performance.

Increasing host plant quality affects higher trophic level predators, but whether such changes are simply a result of prey density or are also affected by changes in prey quality remain uncertain. Moreover, whether changes in prey quality affect measures of predator performance is understudied. Using a combination of field and greenhouse mesocosm experiments, we demonstrate that the survival and body size of a hunting spider (Pardosa littoralis Araneae: Lycosidae) is affected more by prey species identity than the trophic level of the prey. Furthermore, increasing host plant quality does not necessarily propagate through the food web by altering prey quality. While changes in plant quality affected spider body mass, they did so in opposite ways for spiders feeding on Prokelisia (Hemiptera: Delphacodes) herbivores relative to Tytthus (Hemiptera: Miridae) egg predators, and had no impact on spider body mass for two additional species of intraguild prey. These changes in body mass were important because greater body mass increased spider egg production. To examine the generality of this pattern, we reviewed the literature and found a consistent positive relationship between female body size and egg production for Pardosa species, indicating that body size is a reliable proxy for fitness. While many studies emphasize the importance of nitrogen to arthropod diets, this focus may be driven largely by our understanding of herbivore diets rather than predator diets. Thus, the positive impact of host plant quality on higher trophic level predators appears to be driven more by altering prey composition, density, and availability rather than simply providing predators with more nutritious prey.

Predator population size structure alters consumption of prey from epigeic and grazing food webs.

Numerous studies have found that predators can suppress prey densities and thereby impact important ecosystem processes such as plant productivity and decomposition. However, prey suppression by spiders can be highly variable. Unlike predators that feed on prey within a single energy channel, spiders often consume prey from asynchronous energy channels, such as grazing (live plant) and epigeic (soil surface) channels. Spiders undergo few life cycle changes and thus appear to be ideally suited to link energy channels, but ontogenetic diet shifts in spiders have received little attention. For example, spider use of different food channels may be highly specialized in different life stages and thus a species may be a multichannel omnivore only when we consider all life stages. Using stable isotopes, we investigated whether wolf spider (Pardosa littoralis, henceforth Pardosa) prey consumption is driven by changes in spider size. Small spiders obtained > 80% of their prey from the epigeic channel, whereas larger spiders used grazing and epigeic prey almost equally. Changes in prey consumption were not driven by changes in prey density, but by changes in prey use by different spider size classes. Thus, because the population size structure of Pardosa changes dramatically over the growing season, changes in spider size may have important implications for the strength of trophic cascades. Our research demonstrates that life history can be an important component of predator diet, which may in turn affect community- and ecosystem-level processes.

Habitat edge responses of generalist predators are predicted by prey and structural resources.

Generalist predators are thought to be less vulnerable to habitat fragmentation because they use diverse resources across larger spatial scales than specialist predators. Thus, it has been suggested that generalist predators may respond positively to habitat edges or demonstrate no edge response, because they can potentially use prey resources equally well on both sides of the habitat edge. However, most predictions about generalist predator responses to the habitat edge are based solely on prey resources, without consideration of other potential drivers. For instance, structural resources are essential for some species to build webs to capture prey or to avoid intraguild predation and cannibalism. In this study, we used both prey and structural resources to predict the response of four predator functional groups (hunting spiders, web-building spiders, aerial predators, and epigeic predators that feed on the detrital/algal food web) to a habitat edge between two salt-marsh grasses (Spartina alterniflora and Spartina patens). We found that generalist predators largely demonstrated negative responses to the habitat edge and had distinct habitat associations. Positive edge responses were only observed in one functional group (hunting spiders), and this pattern was driven by the two most abundant species. Negative responses to the habitat edge were more common among taxa and were better explained by structural resources rather than prey resources in the two habitats. Although it is generally acknowledged that specialists decline in fragmented habitats, generalists are thought to be more resilient. However, our research demonstrates that even generalists have habitat structural or food resource requirements that may limit their resilience to habitat loss and fragmentation.

What happens when crops are turned on? Simulating constitutive volatiles for tritrophic pest suppression across an agricultural landscape.

BACKGROUND: Herbivore-induced plant volatiles, or HIPVs, are increasingly considered as a biocontrol enhancement tool by constitutively emitting these carnivore-attracting chemicals from agricultural fields. While ample data substantiate the olfactory preference of predators for HIPVs in laboratory environments, little is understood about the consequences of 'turning crops on' in the field. To explore the ramifications for arthropod pest management, a spatially explicit predator-prey population model was constructed that simulated a crop field releasing signals to recruit natural enemies from the surrounding landscape. RESULTS: Field size had an overriding influence on model outcome, both isolated as a single factor and interactively shaping responses to other parameters (e.g. habituation, foraging efficiency). Predator recruitment exponentially declined with increasing field size from nearly double the baseline density in small fields (225 individuals m(-2)) to a mere 4% increase (130 individuals m(-2)) in large fields. Correspondingly, HIPVs enhanced pest consumption in small fields (ca 50% fewer prey), while generating virtually no impact in large fields. CONCLUSION: Collectively, the model suggests that reducing the perimeter/core area ratio will ultimately constrain the utility of predator retention as a pest control tactic in commercial-sized fields and illustrates potential consequences of the widespread commercialization of this technology in agriculture.

Phase I trial of a formulated IL-12 plasmid in combination with carboplatin and docetaxel chemotherapy in the treatment of platinum-sensitive recurrent ovarian cancer.

OBJECTIVES: The primary objective of this study was to evaluate the safety and tolerability of a formulated IL-12 plasmid administered intraperitoneally (IP) in conjunction with intravenous (IV) carboplatin/docetaxel in platinum-sensitive ovarian cancer patients. METHODS: Escalating doses of IL-12 plasmid (phIL-12) formulated with the lipopolymer PEG-PEI-Cholesterol (PPC) were administered IP every 10-11 days for a total of four treatments and the highest dose was expanded to eight treatments. Patients also received IV carboplatin (AUC 5) and docetaxel (75 mg/m(2)) every 21 days. Patients were followed for safety, biological activity and antitumor activity after phIL-12/PPC treatment. RESULTS: All 13 patients enrolled in the study received both phIL-12/PPC and chemotherapy treatment. There were 49 plasmid-associated adverse events (AEs). The most common AEs were abdominal pain, transient hypotension, low grade fever, catheter site pain, chills, dysgeusia, infusion-related reaction, and nausea. These AEs appeared to be plasmid dose related. Grade 3 AEs included manageable abdominal pain and cytokine release syndrome. There were no dose limiting toxicities and the plasmid treatment did not augment the chemotherapy-associated AEs. The best overall antitumor response (17% CR, 33% PR, 42% SD and 8% PD) was typical of the patient population enrolled for the study. Translational studies showed rise in IFN-γ and TNF-α concentrations in a dose dependent manner. CONCLUSIONS: The escalating doses and cycles of intraperitoneal phIL-12/PPC when combined with carboplatin/docetaxel chemotherapy in recurrent ovarian cancer patients were well tolerated and did not appear to exacerbate the side effects or attenuate the efficacy of the chemotherapy treatment.

Predator hunting mode influences patterns of prey use from grazing and epigeic food webs.

Multichannel omnivory by generalist predators, especially the use of both grazing and epigeic prey, has the potential to increase predator abundance and decrease herbivore populations. However, predator use of the epigeic web (soil surface detritus/microbe/algae consumers) varies considerably for reasons that are poorly understood. We therefore used a stable isotope approach to determine whether prey availability and predator hunting style (active hunting vs. passive web-building) impacted the degree of multichannel omnivory by the two most abundant predators on an intertidal salt marsh, both spiders. We found that carbon isotopic values of herbivores remained constant during the growing season, while values for epigeic feeders became dramatically more enriched such that values for the two webs converged in August. Carbon isotopic values for both spider species remained midway between the two webs as values for epigeic feeders shifted, indicating substantial use of prey from both food webs by both spider species. As the season progressed, prey abundance in the grazing food web increased while prey abundance in the epigeic web remained constant or declined. In response, prey consumption by the web-building spider shifted toward the grazing web to a much greater extent than did consumption by the hunting spider, possibly because passive web-capture is more responsive to changes in prey availability. Although both generalist predator species engaged in multichannel omnivory, hunting mode influenced the extent to which these predators used prey from the grazing and epigeic food webs, and could thereby influence the strength of trophic cascades in both food webs.

Nutrient presses and pulses differentially impact plants, herbivores, detritivores and their natural enemies.

Anthropogenic nutrient inputs into native ecosystems cause fluctuations in resources that normally limit plant growth, which has important consequences for associated food webs. Such inputs from agricultural and urban habitats into nearby natural systems are increasing globally and can be highly variable, spanning the range from sporadic to continuous. Despite the global increase in anthropogenically-derived nutrient inputs into native ecosystems, the consequences of variation in subsidy duration on native plants and their associated food webs are poorly known. Specifically, while some studies have examined the effects of nutrient subsidies on native ecosystems for a single year (a nutrient pulse), repeated introductions of nutrients across multiple years (a nutrient press) better reflect the persistent nature of anthropogenic nutrient enrichment. We therefore contrasted the effects of a one-year nutrient pulse with a four-year nutrient press on arthropod consumers in two salt marshes. Salt marshes represent an ideal system to address the differential impacts of nutrient pulses and presses on ecosystem and community dynamics because human development and other anthropogenic activities lead to recurrent introductions of nutrients into these natural systems. We found that plant biomass and %N as well as arthropod density fell after the nutrient pulse ended but remained elevated throughout the nutrient press. Notably, higher trophic levels responded more strongly than lower trophic levels to fertilization, and the predator/prey ratio increased each year of the nutrient press, demonstrating that food web responses to anthropogenic nutrient enrichment can take years to fully manifest themselves. Vegetation at the two marshes also exhibited an apparent tradeoff between increasing %N and biomass in response to fertilization. Our research emphasizes the need for long-term, spatially diverse studies of nutrient enrichment in order to understand how variation in the duration of anthropogenic nutrient subsidies affects native ecosystems.

Do edge responses cascade up or down a multi-trophic food web?

Despite nearly 100 years of edge studies, there has been little effort to document how edge responses 'cascade' to impact multi-trophic food webs. We examined changes within two, four-tiered food webs located on opposite sides of a habitat edge. Based on a 'bottom-up' resource-based model, we predicted plant resources would decline near edges, causing similar declines in specialist herbivores and their associated predators, while a generalist predator was predicted to increase due to complementary resource use. As predicted, we found declines in both specialist herbivores and predators near edges, but, contrary to expectations, this was not driven by gradients in plant resources. Instead, the increase in generalist predators near edges offers one alternative explanation for the observed declines. Furthermore, our results suggest how recent advances in food web theory could improve resource-based edge models, and vice versa.

A seasonal shift in habitat suitability enhances an annual predator subsidy.

1. Entry of substantial numbers of natural enemies from outside a habitat can have profound impacts on food web structure in the recipient habitat, but underlying mechanisms are poorly understood, including the role of relative predator fitness in source and recipient habitats. We studied a naturally occurring annual movement of the salt-marsh spider Pardosa littoralis across habitats in an attempt to clarify factors enhancing and impeding movements of predator populations. 2. Marsh vegetation is dominated by two cordgrass species, Spartina patens, a complex-structured grass with a well-developed litter layer, and Spartina alterniflora, a sparse-structured grass with little thatch accumulation. Pardosa hunts across both habitats and can drastically reduce densities of planthoppers and leafhoppers, the most abundant marsh herbivores. 3. We found an annual subsidy of Pardosa from S. patens, extending hundreds of meters into S. alterniflora made possible by a winter refuge provided by S. patens. As a result, the strength of the subsidy is correlated with the severity of the preceding winter, with the largest subsidies following the coldest winters. 4. Higher Pardosa fitness in the recipient habitat following winter, as indicated by higher growth rates associated with greater prey availability, enhanced the strength of this subsidy. Conversely, lower structural complexity in S. alterniflora, which is associated with higher rates of cannibalism in this spider, may impede the subsidy. 5. The mechanistic underpinnings of the predator subsidy demonstrated here can improve our understanding of subsidies in other contexts, such as conservation biological control. In addition, identifying such subsidies is key to preserving food webs in recipient habitats when source habitats are threatened.

Treatment of disseminated ovarian cancer using nonviral interleukin-12 gene therapy delivered intraperitoneally.

BACKGROUND: The poor prognosis associated with ovarian cancer is primarily the result of delayed diagnosis and the lack of an effective treatment for advanced disease. Use of novel immunotherapy strategies are being evaluated that work to enhance local and systemic immune responses against cancer cells and can possibly work together with traditional cytotoxic chemotherapy regimens to produce more effective treatment options. METHODS: In the present study, we describe a gene-based therapy whereby the anticancer cytokine interleukin-12 gene (pmIL-12) is formulated with a synthetic polymeric delivery vehicle (PPC) and administered intraperitoneally into a mouse model of disseminated ovarian cancer. RESULTS: The administration of pmIL-12/PPC in tumor-bearing mice was associated with a shift towards a Th1 immune state, including significant increases in murine IL-12 (mIL-12) and interferon (IFN)-gamma (mIFN-gamma) in ascites fluid, with little change in systemic levels of these proteins. The mIL-12 protein was detectable for several days and could be reintroduced with subsequent injections. We show that treatment delayed the onset of ascites formation and improved survival in a dose-dependent manner. A significant decrease in vascular endothelial growth factor was associated with pmIL-12/PPC delivery and believed to play a predominant role in inhibiting ascites accumulation. Administration of pmIL-12/PPC was associated with minimal toxicity and, when combined with standard chemotherapies, resulted in additive improvement in survival. CONCLUSIONS: Taken together, these results suggest that pmIL-12/PPC may be an effective strategy for inhibiting progression of disseminated ovarian cancer and may offer a new option for treatment of advanced disease that can be used to complement standard therapies.

Synthesis and application of a non-viral gene delivery system for immunogene therapy of cancer.

The synthesis and gene delivery application of a novel lipopolymer, PEG-PEI-CHOL (PPC), is described. PPC is composed of a low molecular weight branched polyethylenimine (PEI) covalently linked with functional groups methoxypolyethyleneglycol (PEG) and cholesterol (CHOL). The potential utility of PPC as a gene delivery polymer was evaluated by showing its ability to form stable nanocomplexes with DNA, protect DNA from degradation by DNase and mediate gene transfer in vitro and in vivo in solid tumors. The ratio of PEG/PEI/CHOL and nitrogen to phosphate (Polymer/DNA) was optimized for physico-chemical properties and gene delivery efficiency of PPC/DNA complexes. The gene therapy application of the polymer was shown following administration of a murine IL-12 plasmid (pmIL-12) formulated with PPC into tumors in mice which resulted in significant inhibition of tumor growth. The inhibitory effects of pmIL-12/PPC were enhanced when combined with specific chemotherapeutic agents, demonstrating the potential usefulness of pIL-12/PPC as an adjuvant therapy for cancer treatment.

PEGylated insulin in PLGA microparticles. In vivo and in vitro analysis.

A novel controlled release formulation has been developed with PEGylated human insulin encapsulated in PLGA microspheres that produces multi-day release in vivo. The insulin is specifically PEGylated at the amino terminus of the B chain with a relatively low molecular weight PEG (5000 Da). Insulin with this modification retains full biological activity, but has a limited serum half-life, making encapsulation necessary for sustained release beyond a few hours. PEGylated insulin can be co-dissolved with PLGA in methylene chloride and microspheres made by a single o/w emulsion process. Insulin conformation and biological activity are preserved after PEGylation and PLGA encapsulation. The monolithic microspheres have inherently low burst release, an important safety feature for an extended release injectable insulin product. In PBS at 37 degrees C, formulations with a drug content of approximately 14% show very low (< 1%) initial release of insulin over one day and near zero order drug release after a lag of 3-4 days. In animal studies, PEG-insulin microspheres administered subcutaneously as a single injection produced < 1% release of insulin in the first day but then lowered the serum glucose levels of diabetic rats to values < 200 mg/dL for approximately 9 days. When doses were given at 7-day intervals, steady state drug levels were achieved after only 2 doses. PEG-insulin PLGA microparticles show promise as a once-weekly dosed, sustained release basal insulin formulation.