Development of a two-antibody model for the evaluation of copper-64 radioimmunotherapy

Copper‐64 emits β⁺ and β^– particles suitable for positron emission tomography and radioimmunotherapy (RIT) of cancer. Copper‐64‐labelled antibodies have caused complete responses in laboratory animal RIT studies at far lower radiation doses than traditionally prescribed. The intracellular localization of copper radioisotopes may lead to cytotoxic effects by mechanisms beyond ionizing radiation damage. The purpose of this research was to develop a model using both internalizing and non‐internalizing antibodies for direct comparison in future RIT studies using the same animal model of cancer. The monoclonal antibodies, cBR96 and cT84.66, were conjugated with N‐hydroxysulfosuccinimidyl DOTA. All conjugates retained high immunoreactivity and labelled efficiently with ⁶⁴Cu with high specific activity and radiochemical purity. Twenty‐four hour biodistributions determined in LS174T tumour‐bearing nude mice demonstrated low organ and high tumour uptakes for both monoclonal antibodies. This model constitutes a promising system for elucidating whether internalization of ⁶⁴Cu is responsible for an enhanced tumour cytotoxicity in vivo.     

Influence of composition of nutrient medium on the metabolism of chlortoluron in plant-cell suspension cultures

The herbicide chlortoluron readily underwent oxidative metabolism in suspension cultures of cotton and maize. Major attack in cotton cells was by stepwise N-demethylation followed by relatively slow ring-methyl hydroxylation. The most prominent single metabolites seen after 1 day and 7 days were 3-(3-chloro-p-tolyl)urea and its benzyl alcohol analogue, respectively. In maize cells, ring-methyl hydroxylation was apparently the preferred mode of metabolism. Only low amounts of the demethylated derivatives of chlortoluron were evident, and the major residues present at both 2 days and 7 days were the benzyl alcohol derivative of chlortoluron and 3-(3-chloro-4-hydroxymethylphenyl)-1-methylurea. In both species, a substantial proportion of the free ‘phase 1’ metabolites was initially expelled to the medium, but at later times, these were found largely within the cell as polar conjugates. Two approaches were used to examine the influence of the composition of the medium on metabolism. Firstly, cells of both species were grown in four different nutrient media, which were selected to give variation in the organic nutrient and growth factor fraction; secondly, cells were grown in one medium, varying the level of 2, 4-D. In cotton, the rate of metabolism of chlortoluron correlated with the extent to which the four media supported cell growth, Variations were also seen for maize but no correlation with growth rate could be made. For both species, metabolism was retarded when cells were sub-cultured from a medium lacking coconut water to one containing 10% of this supplement. A fifty-fold range in concentration of 2, 4-D had little effect on metabolism in cotton, although a fall-off in rate occurred at the highest level. However, in maize a marked trend towards accelerated metabolism with increasing content of 2, 4-D up to 20 mg litre^?1 was seen, which was independent of effects on growth. The qualitative nature of chlortoluron metabolism in both species was unperturbed by substantial variations in the composition of the medium.     

Integrated pest management and weed management in the United States and Canada

There is interest in more diverse weed management tactics because of evolved herbicide resistance in important weeds in many US and Canadian crop systems. While herbicide resistance in weeds is not new, the issue has become critical because of the adoption of simple, convenient and inexpensive crop systems based on genetically engineered glyphosate‐tolerant crop cultivars. Importantly, genetic engineering has not been a factor in rice and wheat, two globally important food crops. There are many tactics that help to mitigate herbicide resistance in weeds and should be widely adopted. Evolved herbicide resistance in key weeds has influenced a limited number of growers to include a more diverse suite of tactics to supplement existing herbicidal tactics. Most growers still emphasize herbicides, often to the exclusion of alternative tactics. Application of integrated pest management for weeds is better characterized as integrated weed management, and more typically integrated herbicide management. However, adoption of diverse weed management tactics is limited. Modifying herbicide use will not solve herbicide resistance in weeds, and the relief provided by different herbicide use practices is generally short‐lived at best. More diversity of tactics for weed management must be incorporated in crop systems. © 2014 Society of Chemical Industry     

Evaluating and implementing social–ecological systems: A comprehensive approach to sustainable fisheries

Fisheries sustainability is recognized to have four pillars: ecological, economic, social (including cultural) and institutional (or governance). Although international agreements, and legislation in many jurisdictions, call for implementation of all four pillars of sustainability, the social, economic and institutional aspects (i.e., the “human dimensions”) have not been comprehensively and collectively addressed to date. This study describes a framework for comprehensive fisheries evaluation developed by the Canadian Fisheries Research Network (CFRN) that articulates the full spectrum of ecological, economic, social and institutional objectives required under international agreements, together with candidate performance indicators for sustainable fisheries. The CFRN framework is aimed at practical fisheries evaluation and management and has a relatively balanced distribution of elements across the four pillars of sustainability relative to 10 alternative management decision support tools and indicator scorecards, which are heavily focused on ecological and economic aspects. The CFRN framework has five immediate uses: (a) It can serve as a logic frame for defining management objectives; (b) it can be used to define alternate management options to achieve given objectives; (c) it can serve as a tool for comparing management scenarios/options in decision support frameworks; (d) it can be employed to create a report card for comprehensive fisheries management evaluation; and (e) it is a tool for practical implementation of an integrated social–ecological system approach.     

Projecting species distributions using fishery-dependent data

Many marine species are shifting their distributions in response to changing ocean conditions, posing significant challenges and risks for fisheries management. Species distribution models (SDMs) are used to project future species distributions in the face of a changing climate. Information to fit SDMs generally comes from two main sources: fishery-independent (scientific surveys) and fishery-dependent (commercial catch) data. A concern with fishery-dependent data is that fishing locations are not independent of the underlying species abundance, potentially biasing predictions of species distributions. However, resources for fishery-independent surveys are increasingly limited; therefore, it is critical we understand the strengths and limitations of SDMs developed from fishery-dependent data. We used a simulation approach to evaluate the potential for fishery-dependent data to inform SDMs and abundance estimates and quantify the bias resulting from different fishery-dependent sampling scenarios in the California Current System (CCS). We then evaluated the ability of the SDMs to project changes in the spatial distribution of species over time and compare the time scale over which model performance degrades between the different sampling scenarios and as a function of climate bias and novelty. Our results show that data generated from fishery-dependent sampling can still result in SDMs with high predictive skill several decades into the future, given specific forms of preferential sampling which result in low climate bias and novelty. Therefore, fishery-dependent data may be able to supplement information from surveys that are reduced or eliminated for budgetary reasons to project species distributions into the future.