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Robustness analysis: Deconstructing computational models for ecological theory and applications
(2016)
The design of computational models is path-dependent: the choices made in each step during model development constrain the choices that are available in the subsequent steps. The actual path of model development can be extremely different, even for the same system, because the path depends on the question addressed, the availability of data, and the consideration of specific expert knowledge, in addition to the experience, background, and modelling preferences of the modellers. Thus, insights from different models are practically impossible to integrate, which hinders the development of general theory. We therefore suggest augmenting the current culture of communicating models as working just fine with a culture of presenting analyses in which we try to break models, i.e., model mechanisms explaining certain observations break down. We refer to the systematic attempts to break a model as “robustness analysis” (RA). RA is the systematic deconstruction of a model by forcefully changing the model's parameters, structure, and representation of processes. We discuss the nature and elements of RA and provide brief examples. RA cannot be completely formalized into specific techniques and instead corresponds to detective work that is driven by general questions and specific hypotheses, with strong attention focused on unusual behaviours. Both individual modellers and ecological modelling in general will benefit from RA because RA helps with understanding models and identifying “robust theories”, which are general principles that are independent of the idiosyncrasies of specific models. Integrating the results of RAs from different models to address certain systems or questions will then provide a comprehensive overview of when certain mechanisms control system behaviour and when and why this control ceases. This approach can provide insights into the mechanisms that lead to regime shifts in actual ecological systems.
Climate change and land use management practices are major drivers of biodiversity in terrestrial ecosystems. To understand and predict resulting changes in community structures, individual-based and spatially explicit population models are a useful tool but require detailed data sets for each species. More generic approaches are thus needed. Here we present a trait-based functional type approach to model savanna birds. The aim of our model is to explore the response of different bird functional types to modifications in habitat structure. The functional types are characterized by different traits, in particular body mass, which is related to life-history traits (reproduction and mortality) and spatial scales (home range area and dispersal ability), as well as the use of vegetation structures for foraging and nesting, which is related to habitat quality and suitability. We tested the performance of the functional types in artificial landscapes varying in shrub:grass ratio and clumping intensity of shrub patches. We found that an increase in shrub encroachment and a decrease in habitat quality caused by land use mismanagement and climate change endangered all simulated bird functional types. The strength of this effect was related to the preferred habitat. Furthermore, larger-bodied insectivores and omnivores were more prone to extinction due to shrub encroachment compared to small-bodied species. Insectivorous and omnivorous birds were more sensitive to clumping intensity of shrubs whereas herbivorous and carnivorous birds were most affected by a decreasing amount of grass cover. From an applied point of view, our findings emphasize that policies such as woody plant removal and a reduction in livestock stocking rates to prevent shrub encroachment should prioritize the enlargement of existing grassland patches. Overall, our results show that the combination of an individual-based modelling approach with carefully defined functional types can provide a powerful tool for exploring biodiversity responses to environmental changes. Furthermore, the increasing accumulation of worldwide data sets on species’ core and soft traits (surrogates to determine core traits indirectly) on one side and the refinement of conceptual frameworks for animal functional types on the other side will further improve functional type approaches which consider the sensitivities of multiple species to climate change, habitat loss, and fragmentation.
Current rates of environmental change are exceeding the capacity of many populations to adapt to new conditions and thus avoid demographic collapse and ultimate extinction. In particular, cold-water freshwater fish species are predicted to experience strong selective pressure from climate change and a wide range of interacting anthropogenic stressors in the near future. To implement effective management and conservation measures, it is crucial to quantify the maximum rate of change that cold-water freshwater fish populations can withstand. Here, we present a spatially explicit eco-genetic individual-based model, inSTREAM-Gen, to predict the eco-evolutionary dynamics of stream-dwelling trout under anthropogenic environmental change. The model builds on a well-tested demographic model, which includes submodels of river dynamics, bioenergetics, and adaptive habitat selection, with a new genetic module that allows exploration of genetic and life-history adaptations to new environments. The genetic module models the transmission of two key traits, size at emergence and maturity size threshold. We parameterized the model for a brown trout (Salmo trutta L.) population at the warmest edge of its range to validate it and analyze its sensitivity to parameters under contrasting thermal profiles. To illustrate potential applications of the model, we analyzed the population's demographic and evolutionary dynamics under scenarios of (1) climate change-induced warming, and (2) warming plus flow reduction resulting from climate and land use change, compared to (3) a baseline of no environmental change. The model predicted severe declines in density and biomass under climate warming. These declines were lower than expected at range margins because of evolution towards smaller size at both emergence and maturation compared to the natural evolution under the baseline conditions. Despite stronger evolutionary responses, declining rates were substantially larger under the combined warming and flow reduction scenario, leading to a high probability of population extinction over contemporary time frames. Therefore, adaptive responses could not prevent extinction under high rates of environmental change. Our model demonstrates critical elements of next generation ecological modelling aiming at predictions in a changing world as it accounts for spatial and temporal resource heterogeneity, while merging individual behaviour and bioenergetics with microevolutionary adaptations.
Results: Here, an RNA-guided Cas9 system was optimized to enable efficient multiplex editing in Arabidopsis thaliana. We demonstrate the flexibility of our system for knockout of multiple genes, and to generate heritable large-fragment deletions in the genome. As a proof of concept, the function of part of the second intron of the flower development gene AGAMOUS in Arabidopsis was studied by generating a Cas9-free mutant plant line in which part of this intron was removed from the genome. Further analysis revealed that deletion of this intron fragment results 40 % decrease of AGAMOUS gene expression without changing the splicing of the gene which indicates that this regulatory region functions as an activator of AGAMOUS gene expression. Conclusions: Our modified RNA-guided Cas9 system offers a versatile tool for the functional dissection of coding and non-coding DNA sequences in plants.
Formate dehydrogenases (FDHs) are capable of performing the reversible oxidation of formate and are enzymes of great interest for fuel cell applications and for the production of reduced carbon compounds as energy sources from CO2. Metal containing FDHs in general contain a highly conserved active site, comprising a molybdenum (or tungsten) center coordinated by two molybdopterin guanine dinucleotide molecules, a sulfido and a (seleno-)cysteine ligand, in addition to a histidine and arginine residue in the second coordination sphere. So far, the role of these amino acids in catalysis has not been studied in detail, because of the lack of suitable expression systems and the lability or oxygen sensitivity of the enzymes. Here, the roles of these active site residues is revealed using the Mo-containing FDH from Rhodobacter capsulatus. Our results show that the cysteine ligand at the Mo ion is displaced by the formate substrate during the reaction, the arginine has a direct role in substrate binding and stabilization, and the histidine elevates the pK(a) of the active site cysteine. We further found that in addition to reversible formate oxidation, the enzyme is further capable of reducing nitrate to nitrite. We propose a mechanistic scheme that combines both functionalities and provides important insights into the distinct mechanisms of C-H bond cleavage and oxygen atom transfer catalyzed by formate dehydrogenase.
Recently pharmaceuticals have become significant environmental pollutants in aquatic ecosystems, that could affect primary producers such as microalgae. Here we analyzed the effect of pharmaceuticals on the photosynthesis of microalgae commonly found in freshwater-two species of Chlorophyceae and a member of the Eustigmatophyceae, via PAM fluorometry. As pharmaceuticals, three medicines often consumed in households were chosen: (i) fluoxetine, an antidepressant, (ii) propranolol, a beta-blocker and (iii) ibuprofen, an anti-inflammatory and analgesic medicine. The EC50 for the quantum yield of photosystem II in phytoplankton acclimated to inorganic phosphorus (P-i)-replete and P-i-limited conditions was estimated. Acute toxicity experiments over a 5 h exposure revealed that Nannochloropsis limnetica was the least sensitive to pharmaceuticals in its photosynthetic yield out of all species tested. Although the estimation of sub-lethal effects can be vital in contrast to that of LC(50)s, the EC50 values in all species and for all medicines were orders of magnitude higher than concentrations found in polluted surface water. Chlamydomonas reinhardtii was the most sensitive to fluoxetine (EC50 of 1.6 mg L-1), and propranolol (EC50 of 3 mg L-1). Acutodesmus obliquus was most sensitive to ibuprofen (EC50 of 288 mg L-1). Additionally, the sensitivity to the pharmaceuticals changed under a P-i-limitation; the green algae became less sensitive to fluoxetine and propranolol. In contrast, P-i-limited algal species were more sensitive to ibuprofen. Our results suggest that the sensitivity of algae to pharmaceuticals is (i) highly compound- and species-specific and (ii) dependent on the cellular P status.
Recruitment of European eels (Anguilla anguilla) has declined to the extent that they have been added to the IUCN Red List of Threatened Species. Therefore, it is critical to ensure that eels complete their outward river migration in order to contribute to the available spawning stock. We conducted a 4-year (2007-2011) telemetry study to understand the migratory behaviour and potential impact of environmental factors on the eel during this critical life stage. Out of 399 female eels tagged with acoustic transmitters, only 28% demonstrated clear downstream migratory behaviour. Fifty-five percent were detected exhibiting no downstream migration behaviour and 17% were not detected at any monitoring station. Movement patterns of downstream-migrating (silver) eels were characterized by nocturnal activity and seasonal migration, with distinct peaks in autumn and spring. Migration was often discontinuous and exhibited phases of active locomotion and expanded stopovers. The most important determinants of movement activity were water temperature, cumulative precipitation and moonlight, although the significance varied by season and location in the river basin. Our results evidence a discontinuous, stepwise migration over an extended period. Furthermore, our findings indicate that migration success depends on holding duration prior to tagging and environmental predictors with varying importance depending on the season, as well as the locations of capture, tagging and release. Copyright (c) 2015 John Wiley & Sons, Ltd.
Transposable elements (TEs) make up a large proportion of eukaryotic genomes. As their mobilization creates genetic variation that threatens genome integrity, TEs are epigenetically silenced through several pathways, and this may spread to neighboring sequences. JUMONJI (JMJ) proteins can function as antisilencing factors and prevent silencing of genes next to TEs. Whether TE silencing is counterbalanced by the activity of antisilencing factors is still unclear. Here, we characterize JMJ24 as a regulator of TE silencing. We show that loss of JMJ24 results in increased silencing of the DNA transposon AtMu1c, while overexpression of JMJ24 reduces silencing. JMJ24 has a JumonjiC (JmjC) domain and two RING domains. JMJ24 autoubiquitinates in vitro, demonstrating E3 ligase activity of the RING domain(s). JMJ24-JmjC binds the N-terminal tail of histone H3, and full-length JMJ24 binds histone H3 in vivo. JMJ24 activity is anticorrelated with histone H3 Lys 9 dimethylation (H3K9me2) levels at AtMu1c. Double mutant analyses with epigenetic silencing mutants suggest that JMJ24 antagonizes histone H3K9me2 and requires H3K9 methyltransferases for its activity on AtMu1c. Genome-wide transcriptome analysis indicates that JMJ24 affects silencing at additional TEs. Our results suggest that the JmjC domain of JMJ24 has lost demethylase activity but has been retained as a binding domain for histone H3. This is in line with phylogenetic analyses indicating that JMJ24 (with the mutated JmjC domain) is widely conserved in angiosperms. Taken together, this study assigns a role in TE silencing to a conserved JmjC-domain protein with E3 ligase activity, but no demethylase activity.
Both dispersal and local demographic processes determine a population's distribution among habitats of varying quality, yet most theory, experiments, and field studies have focused on the former. We use a generic model to show how both processes contribute to a population's distribution, and how the relative importance of each mechanism depends on scale. In contrast to studies only considering habitat-dependent dispersal, we show that predictions of ideal free distribution (IFD) theory are relevant even at landscape scales, where the assumptions of IFD theory are violated. This is because scales that inhibit one process, promote the other's ability to drive populations to the IFD. Furthermore, because multiple processes can generate IFDs, the pattern alone does not specify a causal mechanism. This is important because populations with IFDs generated by dispersal or demography respond much differently to shifts in resource distributions.
Tula virus (TULV) is a vole-associated hantavirus with low or no pathogenicity to humans. In the present study, 686 common voles (Microtus arvalis), 249 field voles (Microtus agrestis) and 30 water voles (Arvicola spec.) were collected at 79 sites in Germany, Luxembourg and France and screened by RT-PCR and TULV-IgG ELISA. TULV-specific RNA and/or antibodies were detected at 43 of the sites, demonstrating a geographically widespread distribution of the virus in the studied area. The TULV prevalence in common voles (16.7 %) was higher than that in field voles (9.2 %) and water voles (10.0 %). Time series data at ten trapping sites showed evidence of a lasting presence of TULV RNA within common vole populations for up to 34 months, although usually at low prevalence. Phylogenetic analysis demonstrated a strong genetic structuring of TULV sequences according to geography and independent of the rodent species, confirming the common vole as the preferential host, with spillover infections to co-occurring field and water voles. TULV phylogenetic clades showed a general association with evolutionary lineages in the common vole as assessed by mitochondrial DNA sequences on a large geographical scale, but with local-scale discrepancies in the contact areas.
Epigenetic mechanisms convey environmental information through generations and can regulate gene expression. Epigenetic studies in wild mammals are rare, but enable understanding adaptation processes as they may occur in nature. In most wild mammal species, males are the dispersing sex and thus often have to cope with differing habitats and thermal changes more rapidly than the often philopatric females. As temperature is a major environmental selection factor, we investigated whether genetically heterogeneous Wild guinea pig (Cavia aperea) males adapt epigenetically to an increase in temperature, whether that response will be transmitted to the next generation(s), and whether it regulates mRNA expression. Five (F0) adult male guinea pigs were exposed to an increased ambient temperature for 2 months, corresponding to the duration of the species' spermatogenesis. To study the effect of heat, we focused on the main thermoregulatory organ, the liver. We analyzed CpG-methylation changes of male offspring (F1) sired before and after the fathers' heat treatment (as has recently been described in Weyrich et al. [Mol. Ecol., 2015]). Transcription analysis was performed for the three genes with the highest number of differentially methylated changes detected: the thermoregulation gene Signal Transducer and Activator of Transcription 3 (Stat3), the proteolytic peptidase gene Cathepsin Z (Ctsz), and Sirtuin 6 (Sirt6) with function in epigenetic regulation. Stat3 gene expression was significantly reduced (P < 0.05), which indicated a close link between CpG-methylation and expression levels for this gene. The two other genes did not show gene expression changes. Our results indicate the presence of a paternal transgenerational epigenetic effect. Quick adaptation to climatic changes may become increasingly relevant for the survival of wildlife species as global temperatures are rising.
Molecularly imprinted polymers (MIPs) for the recognition of proteins are expected to possess high affinity through the establishment of multiple interactions between the polymer matrix and the large number of functional groups of the target. However, while highly affine recognition sites need building blocks rich in complementary functionalities to their target, such units are likely to generate high levels of nonspecific binding. This paradox, that nature solved by evolution for biological receptors, needs to be addressed by the implementation of new concepts in molecular imprinting of proteins. Additionally, the structural variability, large size and incompatibility with a range of monomers made the development of protein MIPs to take a slow start. While the majority of MIP preparation methods are variants of chemical polymerization, the polymerization of electroactive functional monomers emerged as a particularly advantageous approach for chemical sensing application. Electropolymerization can be performed from aqueous solutions to preserve the natural conformation of the protein templates, with high spatial resolution and electrochemical control of the polymerization process. This review compiles the latest results, identifying major trends and providing an outlook on the perspectives of electrosynthesised protein-imprinted MIPs for chemical sensing. (C) 2016 Elsevier B.V. All rights reserved.
Monoclonal antibodies are highly valuable tools in biomedicine but the generation by hybridoma technology is very time-consuming and elaborate. In order to circumvent the consisting drawbacks an in vitro immunization approach was established by which murine as well as human monoclonal antibodies against a viral coat protein could be developed. The in vitro immunization process was performed by isolation of murine hematopoietic stem cells or human monocytes and an in vitro differentiation into immature dendritic cells. After antigen loading the cells were co-cultivated with naive T and B lymphocytes for three days in order to obtain antigen-specific B lymphocytes in culture, followed by fusion with murine myeloma cells or human/murine heteromyeloma cells. Antigen-specific hybridomas were selected and the generated antibodies were purified and characterized in this study by ELISA, western blot, gene sequencing, affinity measurements. Further the characteristics were compared to a monoclonal antibody against the same target generated by conventional hybridoma technology. Isotype detection revealed a murine IgM and a human IgG4 antibody in comparison to an IgG1 for the conventionally generated antibody. The antibodies derived from in vitro immunization showed indeed a lower affinity for the antigen as compared to the conventionally generated one, which is probably based on the significantly shorter B cell maturation (3 days) during the immunization process. Nevertheless, they were suitable for building up a sandwich based detection system. Therefore, the in vitro immunization approach seems to be a good and particularly fast alternative to conventional hybridoma technology.
Pancreatic secretory zymogen-granule membrane glycoprotein 2 (GP2) has been identified to be a major autoantigenic target in Crohn’s disease patients. It was discussed recently that a long and a short isoform of GP2 exists whereas the short isoform is often detected by GP2-specific autoantibodies. In the outcome of inflammatory bowel diseases, these GP2-specific autoantibodies are discussed as new serological markers for diagnosis and therapeutic monitoring. To investigate this further, camelid nanobodies were generated by phage display and selected against the short isoform of GP2 in order to isolate specific tools for the discrimination of both isoforms. Nanobodies are single domain antibodies derived from camelid heavy chain only antibodies and characterized by a high stability and solubility. The selected candidates were expressed, purified and validated regarding their binding properties in different enzyme-linked immunosorbent assays formats, immunofluorescence, immunohistochemistry and surface plasmon resonance spectroscopy. Four different nanobodies could be selected whereof three recognize the short isoform of GP2 very specifically and one nanobody showed a high binding capacity for both isoforms. The KD values measured for all nanobodies were between 1.3 nM and 2.3 pM indicating highly specific binders suitable for the application as diagnostic tool in inflammatory bowel disease.
The spherical vaterite CaCO3 microcrystals are nowadays widely used as sacrificial templates for fabrication of various microcarriers made of biopolymers (e.g., proteins, nucleic acids, enzymes) due to porous structure and mild template elimination conditions. Here, we demonstrated for the first time that polymer microcarriers with tuned internal nanoarchitecture can be designed by employing the CaCO3 crystals of controlled porosity. The layer-by-layer deposition has been utilized to assemble shell-like (hollow) and matrix-like (filled) polymer capsules due to restricted and free polymer diffusion through the crystal pores, respectively. The crystal pore size in the range of few tens of nanometers can be adjusted without any additives by variation of the crystal preparation temperature in the range 745 degrees C. The temperature-mediated growth mechanism is explained by the Ostwald ripening of nanocrystallites forming the crystal secondary structure. Various techniques including SEM, AFM, CLSM, Raman microscopy, nitrogen adsorptiondesorption, and XRD have been employed for crystal and microcapsule analysis. A three-dimensional model is introduced to describe the crystal internal structure and predict the pore cutoff and available surface for the pore diffusing molecules. Inherent biocompatibility of CaCO3 and a possibility to scale the porosity in the size range of typical biomacromolecules make the CaCO3 crystals extremely attractive tools for template assisted designing tailor-made biopolymer-based architectures in 2D to 3D targeted at drug delivery and other bioapplications.
The importance of intraspecific trait variability for community dynamics and ecosystem functioning has been underappreciated. There are theoretical reasons for predicting that species that differ in intraspecific trait variability will also differ in their effects on ecosystem functioning, particularly in variable environments. We discuss whether species with greater trait variability are likely to exhibit greater temporal stability in their population dynamics, and under which conditions this might lead to stability in ecosystem functioning. Resolving this requires us to consider several questions. First, are species with high levels of variation for one trait equally variable in others? In particular, is variability in response and effects traits typically correlated? Second, what is the relative contribution of local adaptation and phenotypic plasticity to trait variability? If local adaptation dominates, then stability in function requires one of two conditions: (i) individuals of appropriate phenotypes present in the environment at high enough frequencies to allow for populations to respond rapidly to the changing environment, and (ii) high levels of dispersal and gene flow. While we currently lack sufficient information on the causes and distribution of variability in functional traits, filling in these key data gaps should increase our ability to predict how changing biodiversity will alter ecosystem functioning.
Background: Antiphospholipid antibodies (aPL) can be detected in asymptomatic carriers and infectious patients. The aim was to investigate whether a novel line immunoassay (LIA) differentiates between antiphospholipid syndrome (APS) and asymptomatic aPL+ carriers or patients with infectious diseases (infectious diseases controls (IDC)). Methods: Sixty-one patients with APS (56 primary, 22/56 with obstetric events only, and 5 secondary), 146 controls including 24 aPL+ asymptomatic carriers and 73 IDC were tested on a novel hydrophobic solid phase coated with cardiolipin (CL), phosphatic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, beta2-glycoprotein I (beta 2GPI), prothrombin, and annexin V. Samples were also tested by anti-CL and anti-beta 2GPI ELISAs and for lupus anticoagulant activity. Human monoclonal antibodies (humoAbs) against human beta 2GPI or PL alone were tested on the same LIA substrates in the absence or presence of human serum, purified human beta 2GPI or after CL-micelle absorption. Results: Comparison of LIA with the aPL-classification assays revealed good agreement for IgG/IgM a beta 2GPI and aCL. Anti-CL and anti-beta 2GPI IgG/IgM reactivity assessed by LIA was significantly higher in patients with APS versus healthy controls and IDCs, as detected by ELISA. IgG binding to CL and beta 2GPI in the LIA was significantly lower in aPL+ carriers and Venereal Disease Research Laboratory test (VDRL) + samples than in patients with APS. HumoAb against domain 1 recognized beta 2GPI bound to the LIA-matrix and in anionic phospholipid (PL) complexes. Absorption with CL micelles abolished the reactivity of a PL-specific humoAb but did not affect the binding of anti-beta 2GPI humoAbs. Conclusions: The LIA and ELISA have good agreement in detecting aPL in APS, but the LIA differentiates patients with APS from infectious patients and asymptomatic carriers, likely through the exposure of domain 1.
Phenothiazine-modified redox hydrogels were synthesized and used for the wiring of the aldehyde oxidoreductase PaoABC to electrode surfaces. The effects of the pH value and electrode surface modification on the biocatalytic activity of the layers were studied in the presence of vanillin as the substrate. The enzyme electrodes were successfully employed as bioanodes in vanillin/O-2 biofuel cells in combination with a high potential bilirubin oxidase biocathode. Open circuit voltages of around 700 mV could be obtained in a two compartment biofuel cell setup. Moreover, the use of a rather hydrophobic polymer with a high degree of crosslinking sites ensures the formation of stable polymer/enzyme films which were successfully used as bioanode in membrane-less biofuel cells. (C) 2015 Elsevier B.V. All rights reserved.
Interactions between plants and soil microorganisms influence individual plant performance and thus plant-community composition. Most studies on such plant-soil feedbacks (PSFs) have been performed under controlled greenhouse conditions, whereas no study has directly compared PSFs under greenhouse and natural field conditions. We grew three grass species that differ in local abundance in grassland communities simultaneously in the greenhouse and field on field-collected soils either previously conditioned by these species or by the general grassland community. As soils in grasslands are typically conditioned by mixes of species through the patchy and heterogeneous plant species’ distributions, we additionally compared the effects of species-specific versus non-specific species conditioning on PSFs in natural and greenhouse conditions. In almost all comparisons PSFs differed between the greenhouse and field. In the greenhouse, plant growth in species-specific and non-specific soils resulted in similar effects with neutral PSFs for the most abundant species and positive PSFs for the less abundant species. In contrast, in the field all grass species tested performed best in non-specific plots, whereas species-specific PSFs were neutral for the most abundant and varied for the less abundant species. This indicates a general beneficial effect of plant diversity on PSFs in the field. Controlled greenhouse conditions might provide valuable insights on the nominal effects of soils on plants. However, the PSFs observed in greenhouse conditions may not be the determining drivers in natural plant communities where their effects may be overwhelmed by the diversity of abiotic and biotic above- and belowground interactions in the field.