An expression signature of the angiogenic response in gastrointestinal neuroendocrine tumours: correlation with tumour phenotype and survival outcomes.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are heterogeneous with respect to biological behaviour and prognosis. As angiogenesis is a renowned pathogenic hallmark as well as a therapeutic target, we aimed to investigate the prognostic and clinico-pathological role of tissue markers of hypoxia and angiogenesis in GEP-NETs. METHODS: Tissue microarray (TMA) blocks were constructed with 86 tumours diagnosed from 1988 to 2010. Tissue microarray sections were immunostained for hypoxia inducible factor 1α (Hif-1α), vascular endothelial growth factor-A (VEGF-A), carbonic anhydrase IX (Ca-IX) and somatostatin receptors (SSTR) 1–5, Ki-67 and CD31. Biomarker expression was correlated with clinico-pathological variables and tested for survival prediction using Kaplan–Meier and Cox regression methods. RESULTS: Eighty-six consecutive cases were included: 51% male, median age 51 (range 16–82), 68% presenting with a pancreatic primary, 95% well differentiated, 51% metastatic. Higher grading (P=0.03), advanced stage (P<0.001), high Hif-1α and low SSTR-2 expression (P=0.03) predicted for shorter overall survival (OS) on univariate analyses. Stage, SSTR-2 and Hif-1α expression were confirmed as multivariate predictors of OS. Median OS for patients with SSTR-2+/Hif-1α-tumours was not reached after median follow up of 8.8 years, whereas SSTR-2-/Hif-1α+ GEP-NETs had a median survival of only 4.2 years (P=0.006). CONCLUSION: We have identified a coherent expression signature by immunohistochemistry that can be used for patient stratification and to optimise treatment decisions in GEP-NETs independently from stage and grading. Tumours with preserved SSTR-2 and low Hif-1α expression have an indolent phenotype and may be offered less aggressive management and less stringent follow up

Altruism can proliferate through group/kin selection despite high random gene flow

The ways in which natural selection can allow the proliferation of cooperative behavior have long been seen as a central problem in evolutionary biology. Most of the literature has focused on interactions between pairs of individuals and on linear public goods games. This emphasis led to the conclusion that even modest levels of migration would pose a serious problem to the spread of altruism in group structured populations. Here we challenge this conclusion, by analyzing evolution in a framework which allows for complex group interactions and random migration among groups. We conclude that contingent forms of strong altruism can spread when rare under realistic group sizes and levels of migration. Our analysis combines group-centric and gene-centric perspectives, allows for arbitrary strength of selection, and leads to extensions of Hamilton's rule for the spread of altruistic alleles, applicable under broad conditions.Comment: 5 pages, 2 figures. Supplementary material with 50 pages and 26 figure

Bayesian modeling of recombination events in bacterial populations

Background: We consider the discovery of recombinant segments jointly with their origins within multilocus DNA sequences from bacteria representing heterogeneous populations of fairly closely related species. The currently available methods for recombination detection capable of probabilistic characterization of uncertainty have a limited applicability in practice as the number of strains in a data set increases. Results: We introduce a Bayesian spatial structural model representing the continuum of origins over sites within the observed sequences, including a probabilistic characterization of uncertainty related to the origin of any particular site. To enable a statistically accurate and practically feasible approach to the analysis of large-scale data sets representing a single genus, we have developed a novel software tool (BRAT, Bayesian Recombination Tracker) implementing the model and the corresponding learning algorithm, which is capable of identifying the posterior optimal structure and to estimate the marginal posterior probabilities of putative origins over the sites. Conclusion: A multitude of challenging simulation scenarios and an analysis of real data from seven housekeeping genes of 120 strains of genus Burkholderia are used to illustrate the possibilities offered by our approach. The software is freely available for download at URL http://web.abo.fi/fak/ mnf//mate/jc/software/brat.html

Evolutionary connectionism: algorithmic principles underlying the evolution of biological organisation in evo-devo, evo-eco and evolutionary transitions

The mechanisms of variation, selection and inheritance, on which evolution by natural selection depends, are not fixed over evolutionary time. Current evolutionary biology is increasingly focussed on understanding how the evolution of developmental organisations modifies the distribution of phenotypic variation, the evolution of ecological relationships modifies the selective environment, and the evolution of reproductive relationships modifies the heritability of the evolutionary unit. The major transitions in evolution, in particular, involve radical changes in developmental, ecological and reproductive organisations that instantiate variation, selection and inheritance at a higher level of biological organisation. However, current evolutionary theory is poorly equipped to describe how these organisations change over evolutionary time and especially how that results in adaptive complexes at successive scales of organisation (the key problem is that evolution is self-referential, i.e. the products of evolution change the parameters of the evolutionary process). Here we first reinterpret the central open questions in these domains from a perspective that emphasises the common underlying themes. We then synthesise the findings from a developing body of work that is building a new theoretical approach to these questions by converting well-understood theory and results from models of cognitive learning. Specifically, connectionist models of memory and learning demonstrate how simple incremental mechanisms, adjusting the relationships between individually-simple components, can produce organisations that exhibit complex system-level behaviours and improve the adaptive capabilities of the system. We use the term “evolutionary connectionism” to recognise that, by functionally equivalent processes, natural selection acting on the relationships within and between evolutionary entities can result in organisations that produce complex system-level behaviours in evolutionary systems and modify the adaptive capabilities of natural selection over time. We review the evidence supporting the functional equivalences between the domains of learning and of evolution, and discuss the potential for this to resolve conceptual problems in our understanding of the evolution of developmental, ecological and reproductive organisations and, in particular, the major evolutionary transitions

Intelligent Monitoring System for Bird Behavior Study

Until now, the best way to obtain relevant information about the behaviour of animals is capturing them. However, the procedure to capture individuals cause them stress and introduces an effect on the measurement that can affect the behaviour of the animals. To solve this problems this paper describes a novel intelligent motoring system for birds breeding in nest boxes. This system is based in a network of smart-nest boxes that allows access to the acquired data all over the world through internet. A prototype of the proposed system has been implemented for the evaluation of a lesser kestrel breeding colony in Southern Spain. This prototype has offered in a short time more valuable information that several years of manual captures. This prototype has demonstrated that the proposed system allows short and log time animal behaviour evaluation without interferences or causing stress.Junta de Andalucía P06-RNM-01712Junta de Andalucía P06-RNM-04588Junta de Andalucía P07-TIC-02476Junta de Andalucía TIC-570

Considering Intra-individual Genetic Heterogeneity to Understand Biodiversity

In this chapter, I am concerned with the concept of Intra-individual Genetic Hetereogeneity (IGH) and its potential influence on biodiversity estimates. Definitions of biological individuality are often indirectly dependent on genetic sampling -and vice versa. Genetic sampling typically focuses on a particular locus or set of loci, found in the the mitochondrial, chloroplast or nuclear genome. If ecological function or evolutionary individuality can be defined on the level of multiple divergent genomes, as I shall argue is the case in IGH, our current genetic sampling strategies and analytic approaches may miss out on relevant biodiversity. Now that more and more examples of IGH are available, it is becoming possible to investigate the positive and negative effects of IGH on the functioning and evolution of multicellular individuals more systematically. I consider some examples and argue that studying diversity through the lens of IGH facilitates thinking not in terms of units, but in terms of interactions between biological entities. This, in turn, enables a fresh take on the ecological and evolutionary significance of biological diversity

Integrated information increases with fitness in the evolution of animats

One of the hallmarks of biological organisms is their ability to integrate disparate information sources to optimize their behavior in complex environments. How this capability can be quantified and related to the functional complexity of an organism remains a challenging problem, in particular since organismal functional complexity is not well-defined. We present here several candidate measures that quantify information and integration, and study their dependence on fitness as an artificial agent ("animat") evolves over thousands of generations to solve a navigation task in a simple, simulated environment. We compare the ability of these measures to predict high fitness with more conventional information-theoretic processing measures. As the animat adapts by increasing its "fit" to the world, information integration and processing increase commensurately along the evolutionary line of descent. We suggest that the correlation of fitness with information integration and with processing measures implies that high fitness requires both information processing as well as integration, but that information integration may be a better measure when the task requires memory. A correlation of measures of information integration (but also information processing) and fitness strongly suggests that these measures reflect the functional complexity of the animat, and that such measures can be used to quantify functional complexity even in the absence of fitness data.Comment: 27 pages, 8 figures, one supplementary figure. Three supplementary video files available on request. Version commensurate with published text in PLoS Comput. Bio

Self Assessment in Insects: Honeybee Queens Know Their Own Strength

Contests mediate access to reproductive opportunities in almost all species of animals. An important aspect of the evolution of contests is the reduction of the costs incurred during intra-specific encounters to a minimum. However, escalated fights are commonly lethal in some species like the honeybee, Apis mellifera. By experimentally reducing honeybee queens' fighting abilities, we demonstrate that they refrain from engaging in lethal contests that typically characterize their reproductive dominance behavior and coexist peacefully within a colony. This suggests that weak queens exploit an alternative reproductive strategy and provides an explanation for rare occurrences of queen cohabitation in nature. Our results further indicate that self-assessment, but not mutual assessment of fighting ability occurs prior to and during the agonistic encounters

Chimpanzees overcome the tragedy of the commons with dominance

Competition over common-pool resources (CPR) is a ubiquitous challenge for social animals. Many species face similar dilemmas, yet our understanding of the evolutionary trajectory of CPR social strategies remains unexplored. Here, we provide a first look at the social strategies of our closest living relatives, chimpanzees (Pan troglodytes), in two novel resource dilemma experiments. Dyads of chimpanzees were presented with renewable resource systems, collapsible at a quantity-dependent threshold. Dyads had to continuously resist overconsumption to maximize collective gains. In study 1, dyads of chimpanzees sustained a renewing juice source. Inequality of juice acquisition between partners predicted sustaining success, indicating that one individual dominated the task while the partner inhibited. Dyads in study 2 fed together on accumulating carrot pieces but could end the accumulation any time by grabbing an immediate selfish source of carrots. Dyads with low tolerance were more successful at collectively sustaining the resource than highly tolerant dyads. Further, the dominant individual was more likely to cause collapse in dyads with low tolerance than dyads with high tolerance. These results indicate that chimpanzees use a dominance-based monopolisation strategy moderated by social tolerance to overcome the tragedy of the commons

Patient-cooperative control increases active participation of individuals with SCI during robot-aided gait training

ABSTRACT: BACKGROUND: Manual body weight supported treadmill training and robot-aided treadmill training are frequently used techniques for the gait rehabilitation of individuals after stroke and spinal cord injury. Current evidence suggests that robot-aided gait training may be improved by making robotic behavior more patient-cooperative. In this study, we have investigated the immediate effects of patient-cooperative versus non-cooperative robot-aided gait training on individuals with incomplete spinal cord injury (iSCI). METHODS: Eleven patients with iSCI participated in a single training session with the gait rehabilitation robot Lokomat. The patients were exposed to four different training modes in random order: During both non-cooperative position control and compliant impedance control, fixed timing of movements was provided. During two variants of the patient-cooperative path control approach, free timing of movements was enabled and the robot provided only spatial guidance. The two variants of the path control approach differed in the amount of additional support, which was either individually adjusted or exaggerated. Joint angles and torques of the robot as well as muscle activity and heart rate of the patients were recorded. Kinematic variability, interaction torques, heart rate and muscle activity were compared between the different conditions. RESULTS: Patients showed more spatial and temporal kinematic variability, reduced interaction torques, a higher increase of heart rate and more muscle activity in the patient-cooperative path control mode with individually adjusted support than in the non-cooperative position control mode. In the compliant impedance control mode, spatial kinematic variability was increased and interaction torques were reduced, but temporal kinematic variability, heart rate and muscle activity were not significantly higher than in the position control mode. CONCLUSIONS: Patient-cooperative robot-aided gait training with free timing of movements made individuals with iSCI participate more actively and with larger kinematic variability than non-cooperative, position-controlled robot-aided gait training