The role of computation in modeling evolution

Artificial life uses computers and formal systems to model and explore the dynamics of evolution. A fundamental question for A-Life concerns the role of computation in these models, and how we are to interpret computer implementations that do not have actual contact with physical systems. In this paper I will discuss how models are seen to explain and predict in philosophy of science and how these ideas apply to A-Life. I will also explore how the notion of an epistemic cut, as defined by H. Pattee, can be realized in a computational model with an artificial physical world.     

Discovering Relations Between Mind,Brain, and Mental Disorders Using Topic Mapping

Neuroimaging research has largely focused on the identification of associations between brain activation and specific mental functions. Here we show that data mining techniques applied to a large database of neuroimaging results can be used to identify the conceptual structure of mental functions and their mapping to brain systems. This analysis confirms many current ideas regarding the neural organization of cognition, but also provides some new insights into the roles of particular brain systems in mental function. We further show that the same methods can be used to identify the relations between mental disorders. Finally, we show that these two approaches can be combined to empirically identify novel relations between mental disorders and mental functions via their common involvement of particular brain networks. This approach has the potential to discover novel endophenotypes for neuropsychiatric disorders and to better characterize the structure of these disorders and the relations between them.     

Genetical Genomics of Behavior: A Novel Chicken Genomic Model for Anxiety Behavior

The identification of genetic variants responsible for behavioral variation is an enduring goal in biology, with wide-scale ramifications, ranging from medical research to evolutionary theory on personality syndromes. Here, we use for the first time a large-scale genetical genomics analysis in the brains of chickens to identify genes affecting anxiety as measured by an open field test. We combine quantitative trait locus (QTL) analysis in 572 individuals and expression QTL (eQTL) analysis in 129 individuals from an advanced intercross between domestic chickens and Red Junglefowl. We identify 10 putative quantitative trait genes affecting anxiety behavior. These genes were tested for an association in the mouse Heterogeneous Stock anxiety (open field) data set and human GWAS data sets for bipolar disorder, major depressive disorder, and schizophrenia. Although comparisons between species are complex, associations were observed for four of the candidate genes in mice and three of the candidate genes in humans. Using a multimodel approach we have therefore identified a number of putative quantitative trait genes affecting anxiety behavior, principally in chickens but also with some potentially translational effects as well. This study demonstrates that chickens are an excellent model organism for the genetic dissection of behavior.     

Ethics in Indigenous Research – Connecting with Community

The challenge for those responsible for funding, brokering and assessing the merit of proposed Indigenous research is to identify and then work co-operatively with appropriate representatives of Indigenous interests in order to increase the flow of benefits from research to Indigenous peoples. Experience in Australia has shown that this is not a straightforward process. In this paper we indicate some reasons why it is important for the research community to broker research with representative Indigenous organisations and to involve Indigenous peoples in the ethical assessment and conduct of research. We then identify some barriers to the achievement of these objectives and outline recently developed interventions from the field of health research that aim to promote a more effective working relationship between Indigenous peoples and members of the research community.

Evolution and Conservation of Central African Biodiversity: Priorities for Future Research and Education in the Congo Basin and Gulf of Guinea

The tropical forests of the Congo Basin and Gulf of Guinea harbor some of the greatest terrestrial and aquatic biological diversity in the world. However, our knowledge of the rich biological diversity of this region and the evolutionary processes that have shaped it remains limited, as is our understanding of the capacity for species to adapt or otherwise respond to current and projected environmental change. In this regard, research efforts are needed to increase current scientific knowledge of this region's biodiversity, identify the drivers of past diversification, evaluate the potential for species to adapt to environmental change and identify key populations for future conservation. Moreover, when evolutionary research is combined with ongoing environmental monitoring efforts, it can also provide an important set of tools for assessing and mitigating the impacts of development activities. Building on a set of recommendations developed at an international workshop held in Gabon in 2011, we highlight major areas for future evolutionary research that could be directly tied to conservation priorities for the region. These research priorities are centered around five disciplinary themes: (1) documenting and discovering biodiversity; (2) identifying drivers of evolutionary diversification; (3) monitoring environmental change; (4) understanding community and ecosystem level processes; (5) investigating the ecology and epidemiology of disease from an evolutionary perspective (evolutionary epidemiology). Furthermore, we also provide an overview of the needs and priorities for biodiversity education and training in Central Africa.     

Development of a predicted physical map of microsatellite locus positions for pinnipeds, with wider applicability to the Carnivora

Understanding genetic variation responsible for phenotypic differences in natural populations is significantly hampered by a lack of genomic data for many species. Levels of variation can, however, be estimated using microsatellite markers, which may be useful for relating individual fitness to genetic diversity. Prior studies have demonstrated correlations between heterozygosity and individual fitness in some species. These correlations are sometimes driven by a subset of markers, and it is unclear whether this is because those markers best reflect genome-wide heterozygosity, or whether they are linked to fitness-related genes. Differentiating between these scenarios is hindered when the genomic location of markers is unknown. Here, we develop a predicted genomic map of pinniped microsatellite loci based on conservation of primary sequence and genomic location between dog, cat and giant panda. We mapped 210 of 260 (81%) microsatellites from pinnipeds to locations in dog, cat and giant panda genomes. Based on the demonstrable synteny between the genomes of closely related taxa within the Carnivora, we use these data to identify those microsatellites with the greatest chance of cross-species amplification success and demonstrate successful amplification of 21 of 26 loci for cat, dog and two seal species. We also demonstrate the potential to identify candidate genes that may underpin the functional relationship with individual fitness. Overall, we show that this approach provides a rapid and robust method to elucidate genome organisation for nonmodel organisms and have established a resource that facilitates further genetic research on pinnipeds that also has wider applicability to other carnivores.     

The academic jungle: ecosystem modelling reveals why women are driven out of research

The number of women studying science and engineering at undergraduate and postgraduate levels has increased markedly in recent decades. However females have lower retention rates than males in these fields, and perform worse on average than men in terms of promotion and common research metrics. Two key differences between men and women are the larger role that women play in childcare and house work in most families, and the narrower window for female fertility. Here we explore how these two factors affect research output by applying a common ecological model to research performance, incorporating part‐time work and the duration of career prior to the onset of part‐time work. The model parameterizes the positive feedback between historical research output (i.e. track record) and current output, and the minimum threshold below which research output declines. We use the model to provide insight into how women (and men) can pursue a career in academia while working part‐time and devoting substantial time to their family. The model suggests that researchers entering a tenure track (teaching and research) role part‐time without an established track record in research will spend longer in the early career phase compared to full‐time academics, researchers without teaching commitments, and those who were beyond the early career phase prior to working part‐time. The results explain some of the mechanisms behind the observed difference between male and female performance in common metrics and the higher participation of women in teaching‐focussed roles. Based on this analysis, we provide strategies for researchers (particularly women) who want to devote substantial time to raising their families while still remaining engaged with their profession. We also identify how university leaders can enable part‐time academics to flourish rather than flounder. In particular, we demonstrate that careless application of metrics is likely to further reduce female participation in research, and so reduce the pool of talent available.     

Protein database and quantitative analysis considerations when integrating genetics and proteomics to compare mouse strains

Decades of genetics research comparing mouse strains has identified many regions of the genome associated with quantitative traits. Microarrays have been used to identify which genes in those regions are differentially expressed and are therefore potentially causal; however, genetic variants that affect probe hybridization lead to many false conclusions. Here we used spectral counting to compare brain striata between two mouse strains. Using strain-specific protein databases, we concluded that proteomics was more robust to sequence differences than microarrays; however, some proteins were still significantly affected. To generate strain-specific databases, we used a complete database that contained all of the putative genetic isoforms for each protein. While the increased proteome coverage in the databases led to a 6.8% gain in peptide assignments compared to a nonredundant database, it also necessitated the development of a strategy for grouping similar proteins due to a large number of shared peptides. Of the 4563 identified proteins (2.1% FDR), there were 1807 quantifiable proteins/groups that exceeded minimum count cutoffs. With four pooled biological replicates per strain, we used quantile normalization, ComBat (a package that adjusts for batch effects), and edgeR (a package for differential expression analysis of count data) to identify 101 differentially expressed proteins/groups, 84 of which had a coding region within one of the genomic regions of interest identified by the Portland Alcohol Research Center.     

Using Co-authorship Networks to Map and Analyse Global Neglected Tropical Disease Research with an Affiliation to Germany

Background

Research on Neglected Tropical Diseases (NTDs) has increased in recent decades, and significant need-gaps in diagnostic and treatment tools remain. Analysing bibliometric data from published research is a powerful method for revealing research efforts, partnerships and expertise. We aim to identify and map NTD research networks in Germany and their partners abroad to enable an informed and transparent evaluation of German contributions to NTD research.

Methodology/Principal Findings

A SCOPUS database search for articles with German author affiliations that were published between 2002 and 2012 was conducted for kinetoplastid and helminth diseases. Open-access tools were used for data cleaning and scientometrics (OpenRefine), geocoding (OpenStreetMaps) and to create (Table2Net), visualise and analyse co-authorship networks (Gephi). From 26,833 publications from around the world that addressed 11 diseases, we identified 1,187 (4.4%) with at least one German author affiliation, and we processed 972 publications for the five most published-about diseases. Of those, we extracted 4,007 individual authors and 863 research institutions to construct co-author networks. The majority of co-authors outside Germany were from high-income countries and Brazil. Collaborations with partners on the African continent remain scattered. NTD research within Germany was distributed among 220 research institutions. We identified strong performers on an individual level by using classic parameters (number of publications, h-index) and social network analysis parameters (betweenness centrality). The research network characteristics varied strongly between diseases.

Conclusions/Significance

The share of NTD publications with German affiliations is approximately half of its share in other fields of medical research. This finding underlines the need to identify barriers and expand Germany’s otherwise strong research activities towards NTDs. A geospatial analysis of research collaborations with partners abroad can support decisions to strengthen research capacity, particularly in low- and middle-income countries, which were less involved in collaborations than high-income countries. Identifying knowledge hubs within individual researcher networks complements traditional scientometric indicators that are used to identify opportunities for collaboration. Using free tools to analyse research processes and output could facilitate data-driven health policies. Our findings contribute to the prioritisation of efforts in German NTD research at a time of impending local and global policy decisions.     

Early warning signals: the charted and uncharted territories

The realization that complex systems such as ecological communities can collapse or shift regimes suddenly and without rapid external forcing poses a serious challenge to our understanding and management of the natural world. The potential to identify early warning signals that would allow researchers and managers to predict such events before they happen has therefore been an invaluable discovery that offers a way forward in spite of such seemingly unpredictable behavior. Research into early warning signals has demonstrated that it is possible to define and detect such early warning signals in advance of a transition in certain contexts. Here, we describe the pattern emerging as research continues to explore just how far we can generalize these results. A core of examples emerges that shares three properties: the phenomenon of rapid regime shifts, a pattern of “critical slowing down” that can be used to detect the approaching shift, and a mechanism of bifurcation driving the sudden change. As research has expanded beyond these core examples, it is becoming clear that not all systems that show regime shifts exhibit critical slowing down, or vice versa. Even when systems exhibit critical slowing down, statistical detection is a challenge. We review the literature that explores these edge cases and highlight the need for (a) new early warning behaviors that can be used in cases where rapid shifts do not exhibit critical slowing down; (b) the development of methods to identify which behavior might be an appropriate signal when encountering a novel system, bearing in mind that a positive indication for some systems is a negative indication in others; and (c) statistical methods that can distinguish between signatures of early warning behaviors and noise.     

Research versus practice: The dilemmas of research ethics in the era of learning health‐care systems

In this article we attempt to answer the question of how the ethical and conceptual framework (ECF) for a learning health‐care system (LHS) affects some of the main controversies in research ethics by addressing five key problems of research ethics: (a) What is the difference between practice and research? (b) What is the relationship between research ethics and clinical ethics? (c) What is the ethical relevance of the principle of clinical equipoise? (d) Does participation in research require a higher standard of informed consent than the practice of medicine? and (e) What ethical principle should take precedence in medicine? These questions allow us to construct two opposite idealized positions on the distinction between research and practice: the integration model and the segregation model of research and practice. We then compare the ECF for an LHS with these two idealized positions. We argue that the ECF for a LHS does not, in fact, solve these problems, but that it is a third, separate position in the relationship between research ethics and clinical ethics. Moreover, we suggest that the ECF for a LHS raises new ethical problems that require additional ethical analysis and justification. Our article contributes to the discussion on the relationship between research ethics and clinical ethics, revealing that although a learning health‐care system may significantly change the landscape of health care, some ethical dilemmas still require resolving on both theoretical and policy‐making levels.     

The quest for a mechanistic understanding of biodiversity–ecosystem services relationships

Ecosystem services (ES) approaches to biodiversity conservation are currently high on the ecological research and policy agendas. However, despite a wealth of studies into biodiversity''s role in maintaining ES (B–ES relationships) across landscapes, we still lack generalities in the nature and strengths of these linkages. Reasons for this are manifold, but can largely be attributed to (i) a lack of adherence to definitions and thus a confusion between final ES and the ecosystem functions (EFs) underpinning them, (ii) a focus on uninformative biodiversity indices and singular hypotheses and (iii) top-down analyses across large spatial scales and overlooking of context-dependency. The biodiversity–ecosystem functioning (B–EF) field provides an alternate context for examining biodiversity''s mechanistic role in shaping ES, focusing on species'' characteristics that may drive EFs via multiple mechanisms across contexts. Despite acknowledgements of a need for B–ES research to look towards underlying B–EF linkages, the connections between these areas of research remains weak. With this review, we pull together recent B–EF findings to identify key areas for future developments in B–ES research. We highlight a means by which B–ES research may begin to identify how and when multiple underlying B–EF relationships may scale to final ES delivery and trade-offs.     

Neurocognitive mechanisms of synesthesia

Synesthesia is a condition in which stimulation of one sensory modality causes unusual experiences in a second, unstimulated modality. Although long treated as a curiosity, recent research with a combination of phenomenological, behavioral, and neuroimaging methods has begun to identify the cognitive and neural basis of synesthesia. Here, we review this literature with an emphasis on grapheme-color synesthesia, in which viewing letters and numbers induces the perception of colors. We discuss both the substantial progress that has been made in the past fifteen years and some open questions. In particular, we focus on debates in the field relating to the neural basis of synesthesia, including the relationship between synesthesia and attention and the role of meaning in synesthetic colors. We propose that some, but probably not all, of these differences can be accounted for by differences in the synesthetes studied and discuss some methodological implications of these individual differences.     

Indicators of transitions in biological systems

In the face of global biodiversity declines, predicting the fate of biological systems is a key goal in ecology. One popular approach is the search for early warning signals (EWSs) based on alternative stable states theory. In this review, we cover the theory behind nonlinearity in dynamic systems and techniques to detect the loss of resilience that can indicate state transitions. We describe the research done on generic abundance‐based signals of instability that are derived from the phenomenon of critical slowing down, which represent the genesis of EWSs research. We highlight some of the issues facing the detection of such signals in biological systems – which are inherently complex and show low signal‐to‐noise ratios. We then document research on alternative signals of instability, including measuring shifts in spatial autocorrelation and trait dynamics, and discuss potential future directions for EWSs research based on detailed demographic and phenotypic data. We set EWSs research in the greater field of predictive ecology and weigh up the costs and benefits of simplicity vs. complexity in predictive models, and how the available data should steer the development of future methods. Finally, we identify some key unanswered questions that, if solved, could improve the applicability of these methods.     

Characterising functionally important and ecologically meaningful genetic diversity using a candidate gene approach

Over the past two decades the fields of molecular ecology and population genetics have been dominated by the use of putatively neutral DNA markers, primarily to resolve spatio-temporal patterns of genetic variation to inform our understanding of population structure, gene flow and pedigree. Recent emphasis in comparative functional genomics, however, has fuelled a resurgence of interest in functionally important genetic variation that underpins phenotypic traits of adaptive or ecological significance. It may prove a major challenge to transfer genomics information from classical model species to examine functional diversity in non-model species in natural populations, but already multiple gene-targeted candidate loci with major effect on phenotype and fitness have been identified. Here we briefly describe some of the research strategies used for isolating and characterising functional genetic diversity at candidate gene-targeted loci, and illustrate the efficacy of some of these approaches using our own studies on red grouse (Lagopus lagopus scoticus). We then review how candidate gene markers have been used to: (1) quantify genetic diversity among populations to identify those depauperate in genetic diversity and requiring specific management action; (2) identify the strength and mode of selection operating on individuals within natural populations; and (3) understand direct mechanistic links between allelic variation at single genes and variance in individual fitness.     

Twenty years of human research ethics committees in the Baltic States

Two decades have passed since the first attempts were made to establish systematic ethical review of human research in the Baltic States. Legally and institutionally much has changed. In this paper we provide an historical and structural overview of ethical review of human research and identify some problems related to the role of ethical review in establishing quality research environment in these countries. Problems connected to (a) public availability of information, (b) management of conflicts of interest, (c) REC composition and motivation of REC members, and (d) differing levels of stringency of ethical review for different types of studies, are identified. Recommendations are made to strengthen cooperation among the Baltic RECs.     

Spontaneous modulation of a dynamic balance between bacterial genomic stability and mutability: roles and molecular mechanisms of the genetic switch

Bacteria need a high degree of genetic stability to maintain their species identities over long evolutionary times while retaining some mutability to adapt to the changing environment.It is a long unanswered question that how bacteria reconcile these seemingly contradictory biological properties.We hypothesized that certain mechanisms must maintain a dynamic balance between genetic stability and mutability for the survival and evolution of bacterial species.To identify such mechanisms,we analyzed bacterial genomes,focusing on the Salmonella mismatch repair(MMR)system.We found that the MMR gene mutL functions as a genetic switch through a slipped-strand mispairing mechanism,modulating and maintaining a dynamic balance between genetic stability and mutability during bacterial evolution.This mechanism allows bacteria to maintain their phylogenetic status,while also adapting to changing environments by acquiring novel traits.In this review,we outline the history of research into this genetic switch,from its discovery to the latest findings,and discuss its potential roles in the genomic evolution of bacteria.     

Conservation implications of the link between biodiversity and ecosystem functioning

The relationship between biodiversity and individual ecosystem processes is often asymptotic, saturating at relatively low levels, with some species contributing more strongly than others. This has cast doubt on arguments for conservation based on maintenance of the functioning of ecosystems. However, we argue that the link between biodiversity and ecosystem functioning is an important additional argument for conservation for several reasons. (1) Although species differ in importance to ecosystem processes, we do not believe that this argues for preservation of just a few species for two reasons: first, it is nearly impossible to identify all species important to the numerous systems and processes on which humans depend; second, the important species themselves may depend on an unknown number of other species in their communities. (2) Arguments for conservation based on ecosystem functioning are complementary to other utilitarian, ethical and aesthetic justifications. No single reason will convince all people or protect all species, however the combination produces a strong case for conservation of biodiversity. (3) Even if the relationship between biodiversity and ecosystem functioning is asymptotic at local spatial scales and in the short term, effects of biodiversity loss are likely to be important at larger temporal and spatial scales. (4) Initial arguments for the importance of biodiversity for ecosystem functioning were largely based on a precautionary approach (points 1-3). However, we are now moving to a scientific position based on accumulating experimental evidence. The future challenge is the integration of this scientific research with policy.     

Flow cytometry in the study of cell death

In this report we present a concise review concerning the use of flow cytometric methods to characterize and differentiate between two different mechanisms of cell death, apoptosis and necrosis. The applications of these techniques to clinical and basic research are also considered. The following cell features are useful to characterize the mode of cell death: (1) activation of an endonuclease in apoptotic cells results in extraction of the low molecular weight DNA following cell permeabilization, which, in turn, leads to their decreased stainability with DNA-specific fluorochromes. Measurements of DNA content make it possible to identify apoptotic cells and to recognize the cell cycle phase specificity of apoptotic process; (2) plasma membrane integrity, which is lost in necrotic but not in apoptotic cells; (3) the decrease in forward light scatter, paralleled either by no change or an increase in side scatter, represent early changes during apoptosis. The data presented indicate that flow cytometry can be applied to basic research of the molecular and biochemical mechanisms of apoptosis, as well as in the clinical situations, where the ability to monitor early signs of apoptosis in some systems may be predictive for the outcome of some treatment protocols.     

Development of the Pet Bereavement Questionnaire

Abstract

The death of a pet can be a significant stressor for some people and is a known risk factor for depression. The Pet Bereavement Questionnaire (PBQ) was developed to fill the need for a brief, acceptable, well-validated instrument for use in studies of the psychological impact of losing a pet. Initial results suggest that the PBQ has good internal reliability (Cronbach's α = 0.87), as well as good construct validity, with three distinct factors reflecting grief, anger and guilt. Grief was found to correlate strongly with pet attachment. The anger and guilt scales, however, correlated with depressive symptoms. The PBQ discriminated between individuals seeking support after pet loss (who would be expected to show higher levels of bereavement) and those who simply acknowledge the recent loss of a pet. We suggest that future research into pet bereavement use this new questionnaire so that the results of different studies can be compared, normative scores can be developed and researchers in this area can use a single instrument with established construct validity. In particular, we hope the PBQ will be used in treatment outcome research to identify high-risk individuals and test the effectiveness of both existing and novel interventions. Moreover, the PBQ could also be used in clinical settings, such as tertiary care veterinary hospitals, to identify pet owners in need of clinical support services.