Boron-Rich Nanoscale Delivery Agents for the Boron Neutron Capture Therapy of Cancer

Nanoscience Poster SessionThe translational research effort in boron neutron capture therapy (BNCT) described below and recently initiated at the University of Missouri International Institute of Nano and Molecular Medicine and the University of Missouri Research Reactor would benefit from collaboration with a research group knowledgeable in modeling human tumors using small animal hosts and cellular biology as it relates to therapeutic results and the treatment of experimental data. The boron-10 (10B) isotope is unique among light elements for its high neutron cross-section and low inherent toxicity. When subjected to relatively benign thermal neutrons, the 10B nucleus undergoes a neutron capture reaction forming an excited 11B species. This unstable nucleus subsequently undergoes essentially instantaneous fission to release 2.4 MeV of kinetic energy in the form of a pair of 7Li3+ and 4He2+ ions, which are confined to the volume of about one cell. Therefore, preferential accumulation of 10B-containing structures within cancerous cells can lead to selective destruction of these cells. This process is more commonly known as Boron Neutron Capture Therapy (BNCT) for cancer. The key to the implementation of this potentially powerful and selective therapy is the delivery of at least 30 parts per million (ppm) of 10B within the tumor tissue while minimizing superfluous 10B within the surrounding healthy tissue. This difference in 10B concentration is often denoted through the boron concentration in tumor to boron concentration in blood ratio, with a higher ratio being preferable. Herein we describe the synthesis and results of biodistribution experiments with two nano-scale boron delivery agents: liposomes and oligomeric phosphate diesters (OPDs). Liposomes, containing both amphiphilic (KC2B9H11(CH2)15CH3, MAC) and hydrophilic (Na3B20H17NH3, TAC) components and ranging in diameter from 30 to 100 nm, showed tumor boron accumulations as high as 50 ppm and tumor to blood ratios over 8. OPDs, ranging in size from 1 to 5 nm in diameter, also exhibited preferential tumor accumulations of 30 ppm at tumor to blood ratios as high as 35 to 1. In both cases, liposomes and OPDs greatly outperformed currently available small boron-containing pharmaceuticals at the same injected dose of 10B. Studies in which OPDs were fluorescently labeled proved their localization within the cellular nucleus, increasing the relative efficacy of these species due to their proximity to the DNA target. In conclusion, both liposomes and OPDs show great promise as nano-sized delivery vehicles for BNCT

Integrating ecosystem services and disservices: insights from plant invasions

There is growing interest in ecosystem disservices, i.e. the negative effects of ecosystems on humans. The focus on disservices has been controversial because of the lack of clarity on how to disentangle ecosystem services and disservices related to human wellbeing. A perspective that considers both services and disservices is needed to inform objective decision-making. We propose a comprehensive typology of ecosystem disservices, and present a framework for integrating ecosystem services and disservices for human wellbeing linked to ecosystem functioning. Our treatment is underpinned by three key assumptions: (1) ecosystem attributes and functions are value-free; (2) the perception of benefits or nuisances are however dependent on societal context, and preferences and actions by societal actors may trigger, enhance or alleviate benefits or nuisances derived from ecosystems; and (3) the notion of disservices must account for the role of human management in assessments of ecosystem values, i.e. the social and technological measures that identify, protect, promote or restore desirable levels of services, and concurrently minimise, mitigate or adapt to disservices. We illustrate our ideas with examples from plant invasions as a complex social-ecological phenomenon

The progress of interdisciplinarity in invasion science

Interdisciplinarity is needed to gain knowledge of the ecology of invasive species and invaded ecosystems, and of the human dimensions of biological invasions. We combine a quantitative literature review with a qualitative historical narrative to document the progress of interdisciplinarity in invasion science since 1950. Our review shows that 92.4% of interdisciplinary publications (out of 9192) focus on ecological questions, 4.4% on social ones, and 3.2% on social–ecological ones. The emergence of invasion science out of ecology might explain why interdisciplinarity has remained mostly within the natural sciences. Nevertheless, invasion science is attracting social–ecological collaborations to understand ecological challenges, and to develop novel approaches to address new ideas, concepts, and invasion-related questions between scholars and stakeholders. We discuss ways to reframe invasion science as a field centred on interlinked social–ecological dynamics to bring science, governance and society together in a common effort to deal with invasions

Quantitative proteomics identifies biomarkers to distinguish pulmonary from head and neck squamous cell carcinomas by immunohistochemistry

The differentiation between a pulmonary metastasis and a newly developed squamous cell carcinoma of the lung in patients with prior head and neck squamous cell carcinoma (HNSCC) is difficult due to a lack of biomarkers but is crucially important for the prognosis and therapy of the affected patient. By using high-resolution mass spectrometry in combination with stable isotope labelling by amino acids in cell culture, we identified 379 proteins that are differentially expressed in squamous cell carcinomas of the lung and the head and neck. Of those, CAV1, CAV2, LGALS1, LGALS7, CK19, and UGDH were tested by mmunohistochemistry on 194 tissue samples (98 lung and 96 HNSCCs). The combination of CAV1 and LGALS7 was able to distinguish the origin of the squamous cell carcinoma with high accuracy (area under the curve 0.876). This biomarker panel was tested on a cohort of 12 clinically classified lung tumours of unknown origin after HNSCC. Nine of those tumours were immunohistochemically classifiable

Biological Flora of the British Isles: Ambrosia artemisiifolia

1. This account presents information on all aspects of the biology of Ambrosia artemisiifolia L. (Common ragweed) that are relevant to understanding its ecology. The main topics are presented within the standard framework of the Biological Flora of the British Isles: distribution, habitat, communities, responses to biotic factors, responses to environment, structure and physiology, phenology, floral and seed characters, herbivores and disease, and history, conservation, impacts and management. 2. Ambrosia artemisiifolia is a monoecious, wind-pollinated, annual herb native to North America whose height varies from 10 cm to 2.5 m, according to environmental conditions. It has erect, branched stems and pinnately lobed leaves. Spike-like racemes of male capitula composed of staminate (male) florets terminate the stems, while cyme-like clusters of pistillate (female) florets are arranged in groups in the axils of main and lateral stem leaves. 3. Seeds require prolonged chilling to break dormancy. Following seedling emergence in spring, the rate of vegetative growth depends on temperature, but development occurs over a wide thermal range. In temperate European climates, male and female flowers are produced from summer to early autumn (July to October). 4. Ambrosia artemisiifolia is sensitive to freezing. Late spring frosts kill seedlings and the first autumn frosts terminate the growing season. It has a preference for dry soils of intermediate to rich nutrient level. 5. Ambrosia artemisiifolia was introduced into Europe with seed imports from North America in the 19th century. Since World War II, it has become widespread in temperate regions of Europe and is now abundant in open, disturbed habitats as a ruderal and agricultural weed. 6. Recently, the North American ragweed leaf beetle (Ophraella communa) has been detected in southern Switzerland and northern Italy. This species appears to have the capacity to substantially reduce growth and seed production of A. artemisiifolia. 7. In heavily infested regions of Europe, A. artemisiifolia causes substantial crop-yield losses and its copious, highly allergenic pollen creates considerable public health problems. There is a consensus among models that climate change will allow its northward and uphill spread in Europe

Therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes for oral cancer in the hamster cheek pouch model

The application of boron neutron capture therapy (BNCT) mediated by liposomes containing 10B-enriched polyhedral borane and carborane derivatives for the treatment of head and neck cancer in the hamster cheek pouch oral cancer model is presented. These liposomes are composed of an equimolar ratio of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine, incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] (MAC) in the bilayer membrane while encapsulating the hydrophilic species Na3[ae-B20H17NH3] (TAC) in the aqueous core. Unilamellar liposomes with a mean diameter of 83 nm were administered i.v. in hamsters. After 48 h, the boron concentration in tumors was 67 ± 16 ppm whereas the precancerous tissue contained 11 ± 6 ppm, and the tumor/normal pouch tissue boron concentration ratio was 10:1. Neutron irradiation giving a 5-Gy dose to precancerous tissue (corresponding to 21 Gy in tumor) resulted in an overall tumor response (OR) of 70% after a 4-wk posttreatment period. In contrast, the beam-only protocol gave an OR rate of only 28%. Once-repeated BNCT treatment with readministration of liposomes at an interval of 4, 6, or 8 wk resulted in OR rates of 70–88%, of which the complete response ranged from 37% to 52%. Because of the good therapeutic outcome, it was possible to extend the follow-up of BNCT treatment groups to 16 wk after the first treatment. No radiotoxicity to normal tissue was observed. A salient advantage of these liposomes was that only mild mucositis was observed in dose-limiting precancerous tissue with a sustained tumor response of 70–88%.Fil: Heber, Elisa Mercedes. Comisión Nacional de Energía Atómica; ArgentinaFil: Hawthorne, M. Frederick. University of Missouri; Estados UnidosFil: Kueffer, Peter J.. University of Missouri; Estados UnidosFil: Garabalino, Marcela Alejandra. Comisión Nacional de Energía Atómica; ArgentinaFil: Thorp, Silvia Inés. Comisión Nacional de Energía Atómica; ArgentinaFil: Pozzi, Emiliano César Cayetano. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Monti Hughes, Andrea. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Maitz, Charles A.. University of Missouri; Estados UnidosFil: Jalisatgi, Satish S.. University of Missouri; Estados UnidosFil: Nigg, David W.. Idaho National Laboratory; Estados UnidosFil: Curotto, Paula. Comisión Nacional de Energía Atómica; ArgentinaFil: Trivillin, Verónica Andrea. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schwint, Amanda Elena. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Explaining people’s perceptions of invasive alien species:A conceptual framework

Human perceptions of nature and the environment are increasingly being recognised as important for environmental management and conservation. Understanding people's perceptions is crucial for understanding behaviour and developing effective management strategies to maintain, preserve and improve biodiversity, ecosystem services and human well-being. As an interdisciplinary team, we produced a synthesis of the key factors that influence people's perceptions of invasive alien species, and ordered them in a conceptual framework. In a context of considerable complexity and variation across time and space, we identified six broad-scale dimensions: (1) attributes of the individual perceiving the invasive alien species; (2) characteristics of the invasive alien species itself; (3) effects of the invasion (including negative and positive impacts, i.e. benefits and costs); (4) socio-cultural context; (5) landscape context; and (6) institutional and policy context. A number of underlying and facilitating aspects for each of these six overarching dimensions are also identified and discussed. Synthesising and understanding the main factors that influence people's perceptions is useful to guide future research, to facilitate dialogue and negotiation between actors, and to aid management and policy formulation and governance of invasive alien species. This can help to circumvent and mitigate conflicts, support prioritisation plans, improve stakeholder engagement platforms, and implement control measures

Does public awareness increase support for invasive species management?:Promising evidence across taxa and landscape types

Management of invasive species often raises substantial conflicts of interest. Since such conflicts can hamper proposed management actions, managers, decision makers and researchers increasingly recognize the need to consider the social dimensions of invasive species management. In this exploratory study, we aimed (1) to explore whether species’ taxonomic position (i.e. animals vs. plants) and type of invaded landscape (i.e. urban vs. nonurban) might influence public perception about the management of invasive species, and (2) to assess the potential of public awareness to increase public support for invasive species management. We reviewed the scientific literature on the conflicts of interest around the management of alien species and administered two-phased questionnaires (before and after providing information on the target species and its management) to members of the public in South Africa and the UK (n = 240). Our review suggests that lack of public support for the management of invasive animals in both urban and non-urban areas derives mainly from moralistic value disagreements, while the management of invasive plants in non-urban areas mostly causes conflicts based on utilitarian value disagreements. Despite these general trends, conflicts are context dependent and can originate from a wide variety of different views. Notably, informing the public about the invasive status and negative impacts of the species targeted for management appeared to increase public support for the management actions. Therefore, our results align with the view that increased public awareness might increase the public support for the management of invasive species, independent of taxonomic position and type of landscape

Topography-driven isolation, speciation and a global increase of endemism with elevation

Aim: Higher-elevation areas on islands and continental mountains tend to be separated by longer distances, predicting higher endemism at higher elevations; our study is the first to test the generality of the predicted pattern. We also compare it empirically with contrasting expectations from hypotheses invoking higher speciation with area, temperature and species richness. Location: Thirty-two insular and 18 continental elevational gradients from around the world. Methods: We compiled entire floras with elevation-specific occurrence information, and calculated the proportion of native species that are endemic (‘percent endemism’) in 100-m bands, for each of the 50 elevational gradients. Using generalized linear models, we tested the relationships between percent endemism and elevation, isolation, temperature, area and species richness. Results: Percent endemism consistently increased monotonically with elevation, globally. This was independent of richness–elevation relationships, which had varying shapes but decreased with elevation at high elevations. The endemism–elevation relationships were consistent with isolation-related predictions, but inconsistent with hypotheses related to area, richness and temperature. Main conclusions: Higher per-species speciation rates caused by increasing isolation with elevation are the most plausible and parsimonious explanation for the globally consistent pattern of higher endemism at higher elevations that we identify. We suggest that topography-driven isolation increases speciation rates in mountainous areas, across all elevations and increasingly towards the equator. If so, it represents a mechanism that may contribute to generating latitudinal diversity gradients in a way that is consistent with both present-day and palaeontological evidence