Physiological dynamics, reproduction-maintenance allocations and life history evolution

Allocation of resources to competing processes of growth, maintenance, or reproduction is arguably a key process driving the physiology of life history trade‐offs and has been shown to affect immune defenses, the evolution of aging, and the evolutionary ecology of offspring quality. Here, we develop a framework to investigate the evolutionary consequences of physiological dynamics by developing theory linking reproductive cell dynamics and components of fitness associated with costly resource allocation decisions to broader life history consequences. We scale these reproductive cell allocation decisions to population‐level survival and fecundity using a life history approach and explore the effects of investment in reproduction or tissue‐specific repair (somatic or reproductive) on the force of selection, reproductive effort, and resource allocation decisions. At the cellular level, we show that investment in protecting reproductive cells increases fitness when reproductive cell maturation rate is high or reproductive cell death is high. At the population level, life history fitness measures show that cellular protection increases reproductive value by differential investment in somatic or reproductive cells and the optimal allocation of resources to reproduction is moulded by this level of investment. Our model provides a framework to understand the evolutionary consequences of physiological processes underlying trade‐offs and highlights the insights to be gained from considering fitness at multiple levels, from cell dynamics through to population growth.</p

A hidden crisis: strengthening the evidence base on the sustainability of rural groundwater supplies: results from a pilot study in Uganda

Extending and sustaining access to rural water supplies remains central to improving the health and livelihoods of poor people, particularly women, in Africa, where 400 million rural inhabitants have no form of utility provided water, and universal access to water hinges on accelerated development of groundwater (UN 2013). The ‘future proofing’ of groundwater investments is therefore vital, especially in the context of global and local trends including demographic shifts, environmental impacts of human activity and climate change (Taylor et al. 2013). The emphasis, in recent years, on accelerating access to new infrastructure has obscured a hidden crisis of failure. More than 30% of sources are non‐functional within a few years of construction (Rietveld et al. 2009, RWSN 2009, Lockwood et al. 2011) and a greater number are seasonal (for example 50% in Sierra Leone) (MoEWR 2012). The accumulated costs to governments, donors, and, above all, rural people, are enormous. The original benefits generated by the new infrastructure – improved health, nutrition, time savings, education, particularly for the poorest – are lost if improved services cannot be sustained. The cumulative effect of rural water supply failure in Africa over the past 20 years has been estimated by the World Bank to represent a lost investment in excess of $1.2 billion. Critically, there is limited data or analysis on why sources are non‐functional and therefore little opportunity to learn from past mistakes. This report provides a summary of the work undertaken by the UK‐funded UPGro research programme ('Unlocking the Potential for Groundwater for the Poor') for sub‐Saharan Africa (SSA) funded by the Natural Environment Research Council (NERC), the Economic and Social Research Council (ESRC) and the Department for International Development (DfID). The Catalyst Grant project ‘A Hidden Crisis’ was aimed at developing a methodology and toolbox to investigate the causes of failure in groundwater‐based water services in SSA, which could form the foundation for more substantial and larger‐scale research in the future to develop a statistically significant evidence base to examine water point functionality and the underlying causes of failure across a range of physical, social, institutional and governance environments in SSA. To test the toolbox and methodology developed, a pilot study was conducted in northeast Uganda Overall, the approach and methods developed in the catalyst project have been shown to make a significant step towards developing a replicable and robust methodology which can be used to generate a systematic evidence base for supply failure. The work has gone a significant way to encapsulating the complexity of the interlinked aspects of the problem, balancing the natural science and engineering (“technical”) aspects of the research with those concerning the ability of communities to manage and maintain their water points (the “social” aspects). The multiplicity of interlinked causes of water point failure was explicitly acknowledged and taken into account through the use of multi‐disciplinary field and analytical methods within the toolbox and in selection of the research team. The multi‐disciplinary methods of investigation used were highly practical and appropriate to the information sought, and based on detailed observational science

A hidden crisis: strengthening the evidence base on the current failure of rural groundwater supplies

New ambitious international goals for universal access to safe drinking water depend critically on the ability of development partners to accelerate and sustain access to groundwater. However, available evidence (albeit fragmented and methodologically unclear) indicates >30% of new groundwater-based supplies are non-functional within a few years of construction. Critically, in the absence of a significant systematic evidence base or analysis on supply failures, there is little opportunity to learn from past mistakes, to ensure more sustainable services can be developed in the future. This work presents a new and robust methodology for investigating the causes of non-functionality, developed by an interdisciplinary team as part of a UK-funded development research project. The approach was successfully piloted within a test study in NE Uganda, and forms a basis for future research to develop a statistically significant systematic evidence base to unravel the underlying causes of failur

A semi-synthetic oligosaccharide conjugate vaccine candidate confers protection against Streptococcus pneumoniae serotype 3 infection

The identification of immunogenic glycotopes that render glycoconjugate vaccines protective is key to improving vaccine efficacy. Synthetic oligosaccharides are an attractive alternative to the heterogeneous preparations of purified polysaccharides that most marketed glycoconjugate vaccines are based on. To investigate the potency of semi-synthetic glycoconjugates, we chose the least-efficient serotype in the current pneumococcal conjugate vaccine Prevnar 13, Streptococcus pneumoniae serotype 3 (ST3). Glycan arrays containing synthetic ST3 repeating unit oligosaccharides were used to screen a human reference serum for antibodies and to define the recognition site of two ST3-specific protective monoclonal antibodies. The glycan array screens identified a tetrasaccharide that was selected for in-depth immunological evaluation. The tetrasaccharide-CRM197 carrier protein conjugate elicited protective immunity as evidenced by opsonophagocytosis assays and protection against pneumonia caused by ST3 in mice. Formulation of the defined protective lead candidate glycotope has to be further evaluated to elicit optimal long-term immunity

A hidden crisis: strengthening the evidence base on the current failures of rural groundwater supplies

New ambitious international goals for universal access to safe drinking water depend critically on the ability of development partners to accelerate and sustain access to groundwater. However, available evidence (albeit fragmented and methodologically unclear) indicates >30% of new groundwater-based supplies are non-functional within a few years of construction. Critically, in the absence of a significant systematic evidence base or analysis on supply failures, there is little opportunity to learn from past mistakes, to ensure more sustainable services can be developed in the future. This work presents a new and robust methodology for investigating the causes of non-functionality, developed by an interdisciplinary team as part of an UPGro catalyst grant. The approach was successfully piloted within a test study in NE Uganda, and forms a basis for future research to develop a statistically significant systematic evidence base to unravel the underlying causes of failure

An energy budget agent-based model of earthworm populations and its application to study the effects of pesticides

Earthworms are important organisms in soil communities and so are used as model organisms in environ-mental risk assessments of chemicals. However current risk assessments of soil invertebrates are based on short-term laboratory studies, of limited ecological relevance, supplemented if necessary by site-specific field trials, which sometimes are challenging to apply across the whole agricultural landscape. Here, we investigate whether population responses to environmental stressors and pesticide exposure can be accurately predicted by combining energy budget and agent-based models (ABMs), based on knowledge of how individuals respond to their local circumstances. A simple energy budget model was implemented within each earthworm Eisenia fetida in the ABM, based on a priori parameter estimates .From broadly accepted physiological principles, simple algorithms specify how energy acquisition and expenditure drive life cycle processes. Each individual allocates energy between maintenance, growth and/or reproduction under varying conditions of food density, soil temperature and soil moisture. When simulating published experiments, good model fits were obtained to experimental data on individual growth, reproduction and starvation. Using the energy budget model as a platform we developed methods to identify which of the physiological parameters in the energy budget model (rates of ingestion, maintenance, growth or reproduction) are primarily affected by pesticide applications, producing four hypotheses about how toxicity acts. We tested these hypotheses by comparing model outputs with published toxicity data on the effects of copper oxychloride and chlorpyrifos on E. fetida. Both growth and reproduction were directly affected in experiments in which sufficient food was provided, whilst maintenance was targeted under food limitation. Although we only incorporate toxic effects at the individual level we show how ABMs can readily extrapolate to larger scales by providing good model fits to field population data. The ability of the presented model to fit the available field and laboratory data for E.fetida demonstrates the promise of the agent-based approach in ecology, by showing how biological knowledge can be used to make ecological inferences. Further work is required to extend the approach to populations of more ecologically relevant species studied at the field scale. Such a model could help extrapolate from laboratory to field conditions and from one set of field conditions to another or from species to species

Reversal of diastereoselectivity in the synthesis of Peptidomimetic 3‑Carboxamide-1,4-benzodiazepin-5-ones

Enantiopure 3-carboxamide-1,4-benzodiazepin-5-ones were synthesized via the Ugi reaction followed by the Staudinger/aza-Wittig or reduction reactions in only two steps. A complete reversal of diastereoselectivity was achieved depending on the cyclization methodology employed. The different orientation of the C3 substituent in our 3-substituted 1,4-benzodiazepin-5-ones with respect to the most studied 1,4-benzodiazepin-2-ones makes them complementary in the development of new drugs because the primary source of binding selectivity of 1,4-benzodiazepines is the selective recognition of ligand conformations by the receptor.Ministerio de Economía y Competitividad, Spain (Project CTQ2012-31611), Junta de Castilla y León, Consejería de Educación y Cultura y Fondo Social Europeo (Project BU246A12-1) and the European Commission, Seventh Framework Programme (Project SNIFFER FP7-SEC-2012-312411)

Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress

Cytogerontology, the science of cellular ageing, originated in 1881 with the prediction by August Weismann that the somatic cells of higher animals have limited division potential. Weismann's prediction was derived by considering the role of natural selection in regulating the duration of an organism's life. For various reasons, Weismann's ideas on ageing fell into neglect following his death in 1914, and cytogerontology has only reappeared as a major research area following the demonstration by Hayflick and Moorhead in the early 1960s that diploid human fibroblasts are restricted to a finite number of divisions in vitro. In this review we give a detailed account of Weismann's theory, and we reveal that his ideas were both more extensive in their scope and more pertinent to current research than is generally recognised. We also appraise the progress which has been made over the past hundred years in investigating the causes of ageing, with particular emphasis being given to (i) the evolution of ageing, and (ii) ageing at the cellular level. We critically assess the current state of knowledge in these areas and recommend a series of points as primary targets for future research

Sex-specific local life-history adaptation in surface- and cave-dwelling Atlantic mollies (Poecilia mexicana)

Cavefishes have long been used as model organisms showcasing adaptive diversification, but does adaptation to caves also facilitate the evolution of reproductive isolation from surface ancestors? We raised offspring of wild-caught surface- and cave-dwelling ecotypes of the neotropical fish Poecilia mexicana to sexual maturity in a 12-month common garden experiment. Fish were raised under one of two food regimes (high vs. low), and this was crossed with differences in lighting conditions (permanent darkness vs. 12:12 h light:dark cycle) in a 2 × 2 factorial design, allowing us to elucidate potential patterns of local adaptation in life histories. Our results reveal a pattern of sex-specific local life-history adaptation: Surface molly females had the highest fitness in the treatment best resembling their habitat of origin (high food and a light:dark cycle), and suffered from almost complete reproductive failure in darkness, while cave molly females were not similarly affected in any treatment. Males of both ecotypes, on the other hand, showed only weak evidence for local adaptation. Nonetheless, local life-history adaptation in females likely contributes to ecological diversification in this system and other cave animals, further supporting the role of local adaptation due to strong divergent selection as a major force in ecological speciation