Robust Control of Evolutionary Dynamics

The application of principles from evolutionary biology has long been used to gain new insights into the progression and clinical control of both infectious diseases and neoplasms. This iterative evolutionary process consists of expansion, diversification and selection within an adaptive landscape - species are subject to random genetic or epigenetic alterations that result in variations; genetic information is inherited through asexual reproduction and strong selective pressures such as therapeutic intervention can lead to the adaptation and expansion of resistant variants. These principles lie at the center of modern evolutionary synthesis and constitute the primary reasons for the development of resistance and therapeutic failure, but also provide a framework that allows for more effective control.

A model system for studying the evolution of resistance and control of therapeutic failure is the treatment of chronic HIV-1 infection by broadly neutralizing antibody (bNAb) therapy. A relatively recent discovery is that a minority of HIV-infected individuals can produce broadly neutralizing antibodies, that is, antibodies that inhibit infection by many strains of HIV. Passive transfer of human antibodies for the prevention and treatment of HIV-1 infection is increasingly being considered as an alternative to a conventional vaccine. However, recent evolution studies have uncovered that antibody treatment can exert selective pressure on virus that results in the rapid evolution of resistance. In certain cases, complete resistance to an antibody is conferred with a single amino acid substitution on the viral envelope of HIV.

The challenges in uncovering resistance mechanisms and designing effective combination strategies to control evolutionary processes and prevent therapeutic failure apply more broadly. We are motivated by two questions: Can we predict the evolution to resistance by characterizing genetic alterations that contribute to modified phenotypic fitness? Given an evolutionary landscape and a set of candidate therapies, can we computationally synthesize treatment strategies that control evolution to resistance?

To address the first question, we propose a mathematical framework to reason about evolutionary dynamics of HIV from computationally derived Gibbs energy fitness landscapes -- expanding the theoretical concept of an evolutionary landscape originally conceived by Sewall Wright to a computable, quantifiable, multidimensional, structurally defined fitness surface upon which to study complex HIV evolutionary outcomes.

To design combination treatment strategies that control evolution to resistance, we propose a methodology that solves for optimal combinations and concentrations of candidate therapies, and allows for the ability to quantifiably explore tradeoffs in treatment design, such as limiting the number of candidate therapies in the combination, dosage constraints and robustness to error. Our algorithm is based on the application of recent results in optimal control to an HIV evolutionary dynamics model and is constructed from experimentally derived antibody resistant phenotypes and their single antibody pharmacodynamics. This method represents a first step towards integrating principled engineering techniques with an experimentally based mathematical model in the rational design of combination treatment strategies and offers predictive understanding of the effects of combination therapies of evolutionary dynamics and resistance of HIV. Preliminary in vitro studies suggest that the combination antibody therapies predicted by our algorithm can neutralize heterogeneous viral populations despite containing resistant mutations.

The role of specially designated wildlife sites in freshwater conservation - an English perspective

The value of specially designated sites in conserving biodiversity has been a hotly debated issue for many years. The debate has recently been given fresh impetus by the creation of Natural England, the new Government Agency responsible for the protection and enhancement of the natural environment in England, and the challenges facing the management of designated sites resulting from the increasingly tangible effects of climate change. In the freshwater environment, the role of designated sites is very much under the spotlight because of the implementation of the European 'Water Framework' Directive, which aspires to holistic, ecologically-based management of aquatic habitats.This paper explores the underlying premises of, and rationale for, special site designations for wildlife, and provides a frank account of the inevitable clash of management philosophies that designated sites create in the freshwater environment, drawing on experiences of managing designated freshwater sites in England over the past decade. A positive role is outlined for designated sites in freshwater conservation, which addresses these management conflicts in a way that not only meets Government obligations towards these sites but also paves the way for enlightened, progressive management of the wider freshwater resource. As part of this account, attempts are made to clarify the relationship between key biodiversity-related policy drivers in the freshwater environment, and to explain how the spectre of climate change can be addressed within designated site management. The importance of strategic freshwater science, collaboratively designed and funded, in maximising the value of the designated freshwater site network to the wider freshwater habitat resource, is stressed.

Using RIVPACS for studies on conservation and biodiversity

Invertebrate conservation relies not only on public support and political will, but also on possessing an adequate understanding of the distribution and ecology of invertebrate species and communities. In the UK, RIVPACS is making an important contribution to assessing the conservation importance of river invertebrate assemblages. So far, work has largely centred on using RIVPACS as an integral part of SERCON (System for Evaluating Rivers for Conservation), in which data collected using the standard RIVPACS method are interpreted with reference to conservation criteria such as species richness and representativeness. Applications of RIVPACS to other areas of conservation - whether providing information on the ecological requirements of rare species, monitoring the success of river restoration projects, or making broader assessments of sustainability - are probably more limited, but merit further examination. It is important to develop closer links between RIVPACS and techniques such as SERCON and RHS (River Habitat Survey) in order to maximise the benefit each can bring tostudies on conservation and biodiversity. It should also be recognised that there are limitations in transferring such systems to other countries where approaches to nature conservation may be very different.

Conservation activity expands captive breeding

From a special issue: A Brief History of the Charles Darwin Foundation for the Galapagos Islands 1959-1988

Early attempts at Galapagos conservation

From a special issue: A Brief History of the Charles Darwin Foundation for the Galapagos Islands 1959-1988

Planning conservation

From a special issue: A Brief History of the Charles Darwin Foundation for the Galapagos Islands 1959-1988

Molecular ecology of european mustelids: Unraveling evolutionary and ecological patterns in Martes and Lutra genera

208 p.

Comunidades vegetais em quatro pães-de-açúcar no Estado do Rio de Janeiro

Os afloramentos rochosos apresentam flora peculiar, sendo constituídos de habitats únicos que podem representar barreira para muitas espécies devido às suas condições ambientais diferenciadas do entorno. O Estudo desse tipo de área pode fornecer informações relevantes sobre o processo evolutivo e distribuição das espécies que ali ocorrem. Esta pesquisa teve como objetivos gerar maiores informações sobre ecologia, florística e conservação de comunidades de moitas em quatro pães-de-açúcar do Estado do Rio de Janeiro. São eles o Maciço do Itaoca (Campos dos Goytacazes), o Costão de Itacoatiara (Niterói), o Morro dos Cabritos do Parque Natural Municipal da Prainha e o Monumento Natural dos Morros da Urca e Pão de Açúcar (Rio de Janeiro). Os resultados são apresentados em duas seções, a primeiro trata da florística, estrutura e relações ambientais desse tipo de vegetação; e a segunda aborda a florística e estado de conservação da flora rupícola de forma geral das quatro áreas de estudo. Para a primeira seção foram distribuídas 72 parcelas de 1m x 1m ao longo de três linhas de 50m em cada área amostrada e registrados dados da presença de cada espécie por parcela, área de cobertura e altura dos indivíduos. Também foi verificado o tipo de substrato e tomadas medidas de declividade e profundidade do solo e serrapilheira. No total foram marcadas 288 parcelas nas quatro áreas. Entre as famílias mais importantes para as quatro áreas estão Cactaceae, Bromeliaceae, Orchidaceae e Asteraceae. Os resultados mostram que entre as espécies apontadas com maiores valores de importância estão entre as que exercem maior peso na ordenação dos grupos florísticos evidenciados pela análise de componentes principais (PCA) para as quatro áreas. Uma análise de redundância (RDA) foi realizada e mostrou que as variáveis que mais parecem influenciar a composição florística das moitas são as mais sujeitas aos processos biológicos e dinâmica da vegetação como um todo. Dados acerca do espectro biológico e índices de diversidade e equabilidade também são apresentados nesta seção. Para a 2 seção foram compiladas informações de herbários e coletas realizadas em campo, formando uma listagem geral com 193 espécies rupícolas para as quatro áreas. São apresentados os dados florísticos da vegetação e sua distribuição geográfica. No total 28 espécies são restritas ao Estado do Rio de Janeiro e 68 são endêmicas da Mata Atlântica. Dentre elas, 26 encontram-se inseridas em alguma categoria de ameaça de extinção. As principais ameaças e impactos sobre a vegetação dessas áreas foram abordados no contexto da conservação da flora rupícola encontrada, dentre elas, as mais significativas são o fogo, a mineração e a abertura de novos acessos em encostas com vegetação abundante.