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Neural Signatures of Prediction Errors in a Decision-making Task are Modulated by Action Execution Failures

Decisions must be implemented through actions, and actions are prone to error. As such, when an expected outcome is not obtained, an individual should not only be sensitive to whether the choice itself was suboptimal, but also whether the action required to indicate that choice was executed successfully. The intelligent assignment of credit to action execution versus action selection has clear ecological utility for the learner. To explore this scenario, we used a modified version of a classic reinforcement learning task in which feedback indicated if negative prediction errors were, or were not, associated with execution errors. Using fMRI, we asked if prediction error computations in the human striatum, a key substrate in reinforcement learning and decision making, are modulated when a failure in action execution results in the negative outcome. Participants were more tolerant of non-rewarded outcomes when these resulted from execution errors versus when execution was successful but the reward was withheld. Consistent with this behavior, a model-driven analysis of neural activity revealed an attenuation of the signal associated with negative reward prediction error in the striatum following execution failures. These results converge with other lines of evidence suggesting that prediction errors in the mesostriatal dopamine system integrate high-level information during the evaluation of instantaneous reward outcomes.

neuroscience

Artificial selection of microbial communities to enhance degradation of recalcitrant polymers

Recalcitrant polymers are widely distributed in the environment. This includes natural polymers, such as chitin, but synthetic polymers are becoming increasingly abundant, for which biodegradation is uncertain. Distribution of labour in microbial communities commonly evolves in nature, particularly for arduous processes, suggesting a community may be better at degrading recalcitrant compounds than individual microorganisms. Artificial selection of microbial communities with better degradation potential has seduced scientists for over a decade, but the method has not been systematically optimised nor applied to polymer degradation. Using chitin as a case study, we successfully selected for microbial communities with enhanced chitinase activities but found that continuous optimisation of incubation times between selective generations was of utmost importance. The analysis of the community composition over the entire selection process revealed fundamental aspects in microbial ecology: when incubation times between generations were optimal, the system was dominated by Gammaproteobacteria, main bearers of chitinase enzymes and drivers of chitin degradation, before being succeeded by cheating, cross-feeding and grazing organisms.\n\nImportanceArtificial selection is a powerful and atractive technique that can enhance the biodegradation of a recalcitrant polymer and other pollutants by microbial communities. We show, for the first time, that the success of artificially selecting microbial communities requires an optimisation of the incubation times between generations when implementing this method. Hence, communities need to be transferred at the peak of the desired activity in order to avoid community drift and replacement of the efficient biodegrading community by cheaters, cross-feeders and grazers.

microbiology

Spatio-temporal dynamics of dengue in Brazil: seasonal travelling waves and determinants of regional synchrony

Dengue continues to be the most important vector-borne viral disease globally and in Brazil, where more than 1.4 million cases and over 500 deaths were reported in 2016. Mosquito control programmes and other interventions have not stopped the alarming trend of increasingly large epidemics in the past few years.\n\nHere, we analyzed monthly dengue cases reported in Brazil between 2001 and 2016 to better characterize the key drivers of dengue epidemics. Spatio-temporal analysis revealed recurring travelling waves of disease occurrence. Using wavelet methods, we characterised the average seasonal pattern of dengue in Brazil, which starts in the western states of Acre and Rondonia, then travels eastward to the coast before reaching the northeast of the country. Only two states in the north of Brazil (Roraima and Amapa) did not follow the countrywide pattern and had inconsistent timing of dengue epidemics throughout the study period.\n\nWe also explored epidemic synchrony and timing of annual dengue cycles in Brazilian regions. Using gravity style models combined with climate factors, we showed that both human mobility and vector ecology contribute to spatial patterns of dengue occurrence.\n\nThis study offers a characterization of the spatial dynamics of dengue in Brazil and its drivers, which could inform intervention strategies against dengue and other arboviruses.\n\nAuthor summaryIn this paper we studied the synchronization of dengue epidemics in Brazilian regions. We found that a typical dengue season in Brazil can be described as a wave travelling from the western part of the country towards the east, with the exception of the two most northern equatorial states that experienced inconsistent seasonality of dengue epidemics.\n\nWe found that the spatial structure of dengue cases is driven by both climate and human mobility patterns. In particular, precipitation was the most important factor for the seasonality of dengue at finer spatial resolutions.\n\nOur findings increase our understanding of large scale dengue patterns and could be used to enhance national control programs against dengue and other arboviruses.

epidemiology

Interrogation of genes controlling biofilm formation using CRISPR interference in Pseudomonas fluorescens

Bacterial biofilm formation involves multigenic signaling and regulatory pathways that control the transition from motile to sessile lifestyle, production of extracellular polymeric matrix, and maturation of the biofilm complex 3D structure. Biofilms are extensively studied because of their importance in biomedical, ecological and industrial settings. Genetic approaches based on gene inactivation are powerful for mechanistic studies but often are labor intensive, limiting systematic gene surveys to the most tractable bacterial hosts. Here, we adapted the CRISPR interference (CRISPRi) system for use in P. fluorescens. We found that CRISPRi is applicable to three genetically and physiologically diverse species, SBW25, WH6 and Pf0-1 and affords extended periods of time to study complex phenotypes such as cell morphology, motility and biofilm formation. In SBW25, CRISPRi-mediated silencing of the GacA/S two-component system and genes regulated by cylic-di-GMP produced phenotypes similar to those previously described after gene inactivation in various Pseudomonas. Combined with detailed confocal microscopy of biofilms, our study also revealed novel phenotypes associated with biofilm architecture and extracellular matrix biosynthesis as well as the potent inhibition of SBW25 biofilm formation mediated by the PFLU1114 protein. Thus, CRISPRi is a reliable and scalable approach to interrogate gene networks in the diverse P. fluorescens group.

microbiology

Towards multi-drug adaptive therapy

A new ecologically inspired paradigm in cancer treatment known as \"adaptive therapy\" capitalizes on competitive interactions between drug-sensitive and drug-resistant subclones. The goal of adaptive therapy is to maintain a controllable stable tumor burden by allowing a significant population of treatment sensitive cells to survive. These, in turn, suppress proliferation of the less fit resistant populations. However, there remain several open challenges in designing adaptive therapies, particularly in extending these therapeutic concepts to multiple treatments. We present a cancer treatment case study (metastatic castrate resistant prostate cancer) as a point of departure to illustrate three novel concepts to aid the design of multi-drug adaptive therapies. First, frequency-dependent \"cycles\" of tumor evolution can trap tumor evolution in a periodic, controllable loop. Second, the availability and selection of treatments may limit the evolutionary \"absorbing region\" reachable by the tumor. Third, the velocity of evolution significantly influences the optimal timing of drug sequences.

cancer biology

The ‘zoo’ accompanying Botryococcus braunii: Unraveling the fundamentals of algae-bacteria biocoenosis

Bacteria occupy all major ecosystems and maintain an intensive relationship to the eukaryotes, developing together into complex biomes (i.e., phycosphere and rhizosphere). Interactions between eukaryotes and bacteria range from cooperative to competitive, with the associated microorganisms affecting their hosts development, growth, health and disease. Since the advent of non-culture dependent analytical techniques such as metagenome sequencing, consortia have been described but owing to the complex interactions rarely functionally dissected. Multifaceted analysis of the microbial consortium of the ancient phytoplankton Botryococcus as an attractive model food web revealed that its all abundant bacterial members belong to a distinct niche of biotin auxotrophs, essentially depending on the microalga. In addition, hydrocarbonoclastic bacteria without vitamin auxotrophies, which adversely affect the algal cell morphology, appear evidently decimated. Synthetic rearrangement of a minimal community consisting of alga, mutualistic and parasitic bacteria underpins the model of a eukaryote that domesticates its own mutualistic bacterial "zoo" to manipulate and control its surrounding biosphere. This model of domestication of mutualistic bacteria for the defense against destruents by a eukaryotic host could represent ecologically relevant interactions that cross species boundaries. Metabolic and system reconstruction disentangles the relationships and provide a blueprint for the construction of mutually beneficial synthetic ecosystems.

microbiology

Selection at behavioral, developmental and metabolic genes is associated with the northward expansion of a successful tropical colonizer

What makes a species able to colonize novel environments? This question is key to understand the dynamics of adaptive radiations and ecological niche shifts, but the mechanisms that underlie expansion into novel habitats remain poorly understood at a genomic scale. Lizards from the genus Anolis are typically tropical and the green anole (Anolis carolinensis) constitutes an exception since it expanded into temperate North America from subtropical Florida. Thus, we used the green anole as a model to investigate signatures of selection associated with colonization of a new environment, namely temperate North America. To this end, we analyzed 29 whole genome sequences, representing the entire genetic diversity of the species. We used a combination of recent methods to quantify both positive and balancing selection in northern populations, including FST outlier methods, machine learning and ancestral recombination graphs. We naively scanned for genes of interest and assessed the overlap between multiple tests. Strikingly, we identified many genes involved in behavior, suggesting that the recent successful colonization of northern environments may have been linked to behavioral shifts as well as physiological adaptation. These results were robust to recombination, gene length and clustering. Using a candidate genes strategy, we determined that genes involved in response to cold or behavior displayed more frequently signals of selection, while controlling for local recombination rate and gene length. In addition, we found signatures of balancing selection at immune genes in all investigated genetic groups, but also at genes involved in neuronal and anatomical development in Florida.

evolutionary biology

Beware the Jaccard: the choice of metric is important and non-trivial in genomic colocalisation analysis.

BackgroundThe generation and systematic collection of genome-wide data is ever-increasing. This vast amount of data has enabled researchers to study relations between a variety of genomic and epigenomic features, including genetic variation, gene regulation, and phenotypic traits. Such relations are typically investigated by comparatively assessing genomic co-occurrence. Technically, this corresponds to assessing the similarity of pairs of genome-wide binary vectors. A variety of metrics have been proposed for this problem in other fields like ecology. However, while several of these metrics have been employed for assessing genomic co-occurrence, their appropriateness for the genomic setting has never been investigated.\n\nResultsWe show that the choice of metric may strongly influence results and propose two alternative modelling assumptions that can be used to guide this choice. On both simulated and real genomic data, the Jaccard index is strongly affected by dataset size and should be used with caution. The Forbes coefficient (fold change) and tetrachoric correlation are less affected by dataset size, but one should be aware of increased variance for small datasets.\n\nAvailabilityAll results on simulated and real data can be inspected and reproduced at: https://hyperbrowser.uio.no/sim-measure

bioinformatics

Charting the diversity of Uncultured Viruses of Archaea and Bacteria

Viruses of Archaea and Bacteria are among the most abundant and diverse biological entities on Earth. Unraveling their biodiversity has been challenging due to methodological limitations. Recent advances in culture-independent techniques, such as metagenomics, shed light on viral dark matter, revealing thousands of new viral genomes at an unprecedented scale. However, these novel genomes have not been properly classified and the evolutionary associations between them were not resolved. Here, we performed phylogenomic analysis of nearly 200,000 viral genomic sequences to establish GL-UVAB: Genomic Lineages of Uncultured Viruses of Archaea and Bacteria. GL-UVAB yielded a 44-fold increase in the amount of classified genomes. The pan-genome content of the identified lineages revealed their infection strategies, potential to modulate host physiology and mechanisms to escape resistance systems. Furthermore, using GL-UVAB for annotating metagenomes from multiple ecosystems revealed elusive habitat distribution patterns of viral communities. These findings expand the understanding of the diversity, evolution and ecology of viruses of prokaryotes.

microbiology

Random Tanglegram Partitions (Random TaPas): An Alexandrian Approach to the Cophylogenetic Gordian Knot

Symbiosis is a key driver of evolutionary novelty and ecological diversity, but our understanding of how macroevolutionary processes originate extant symbiotic associations is still very incomplete. Cophylogenetic tools are used to assess the congruence between the phylogenies of two groups of organisms related by extant associations. If phylogenetic congruence is higher than expected by chance, we conclude that there is cophylogenetic signal in the system under study. However, how to quantify cophylogenetic signal is still an open issue. We present a novel approach, Random Tanglegram Partitions (Random TaPas) that applies a given global-fit method to random partial tanglegrams of a fixed size to identify the associations, terminals and nodes that maximize phylogenetic congruence. By means of simulations, we show that the output value produced is inversely proportional to the number and proportion of cospeciation events employed to build simulated tanglegrams. In addition, with time-calibrated trees, Random TaPas is also efficient at distinguishing cospeciation from pseudocospeciation. Random TaPas can handle large tanglegrams in affordable computational time and incorporates phylogenetic uncertainty in the analyses. We demonstrate its application with two real examples: Passerine birds and their feather mites, and orchids and bee pollinators. In both systems, Random TaPas revealed low cophylogenetic signal, but mapping its variation onto the tanglegram pointed to two different coevolutionary processes. We suggest that the recursive partitioning of the tanglegram buffers the effect of phylogenetic nonindependence occurring in current global-fit methods and therefore Random TaPas is more reliable than regular global-fit methods to identify host-symbiont associations that contribute most to cophylogenetic signal. Random TaPas can be implemented in the public-domain statistical software R with scripts provided herein. A Users Guide is also available at GitHub.

evolutionary biology

Regulatory changes in pterin and carotenoid genes underlie balanced color polymorphisms in the wall lizard

Reptiles use pterin and carotenoid pigments to produce yellow, orange, and red colors. These conspicuous colors serve a diversity of signaling functions, but their molecular basis remains unresolved. Here, we show that the genomes of sympatric color morphs of the European common wall lizard, which differ in orange and yellow pigmentation and in their ecology and behavior, are virtually undifferentiated. Genetic differences are restricted to two small regulatory regions, near genes associated with pterin (SPR) and carotenoid metabolism (BCO2), demonstrating that a core gene in the housekeeping pathway of pterin biosynthesis has been co-opted for bright coloration in reptiles and indicating that these loci exert pleiotropic effects on other aspects of physiology. Pigmentation differences are explained by extremely divergent alleles and haplotype analysis revealed abundant trans-specific allele sharing with other lacertids exhibiting color polymorphisms. The evolution of these conspicuous color ornaments is the result of ancient genetic variation and cross-species hybridization.

evolutionary biology

Vulnerability to climate change for narrowly ranged species: the case of Ecuadorian endemic Magnolia mercedesiarum

Species vulnerability to climate change has been inferred using species distribution models from an example of the recently discovered Magnolia mercedesiarum (sect. Talauma, Magnoliaceae), a narrowly ranged species endemic to moist tropical forests in the eastern Ecuadorian Andes. The environmental conditions within the current species distribution area has been compared with conditions projected to 2050 and 2070, using data from the HadGEM2-ES model in two CO2 emission scenarios: RCP4.5 and RCP8.5. The ecological niche modelling allowed determination of parameters of climatic environmental conditions that control current species distribution to produce a hypothesis on probable changes in spatial pattern of suitable habitats in future scenarios. Within the current species distribution area of M. mercedesiarum, significant reduction of habitat suitability was projected for both emission scenarios, combined with a lack of nearby areas with adequate environmental conditions. Several disjunct sites of high habitat suitability were found to emerge in the Colombian Andes, but they seem unreachable by this tree species in the scope of a few decades, due to intrinsic dispersal limitations. The reduction of habitat suitability and improbability of distribution area shift to adjacent geographic locations could mean a high species vulnerability to climate change. The species could be at risk of extinction if it does not possess hidden phenotypical plasticity and potential for fast adaptation to climate change.

plant biology

A Network based Approach to Identify the Genetic Influence Caused by Associated Factors and Disorders for the Parkinsons Disease Progression

Actual causes of Parkinsons disease (PD) are still unknown. In any case, a better comprehension of genetic and ecological influences to the PD and their interaction will assist physicians and patients to evaluate individual hazard for the PD, and definitely, there will be a possibility to find a way to reduce the progression of the PD. We introduced quantitative frameworks to reveal the complex relationship of various biasing genetic factors for the PD. In this study, we analyzed gene expression microarray data from the PD, ageing (AG), severe alcohol consumption (AC), type II diabetes (T2D), high body fat (HBF), hypercholesterolemia (HC), high dietary fat (HDF), red meat dietary (RMD), sedentary lifestyle (SL), smoking (SM), and control datasets. We have developed genetic associations of various factors with the PD based on the neighborhood-based benchmarking and multilayer network topology.\n\nWe identified 1343 significantly dysregulated genes in the PD patients compared to the healthy control, where we have 779 genes down regulated and 544 genes up regulated. 69 genes were highly expressed in both for the PD and alcohol consumption whereas the number of shared genes for the PD and the type II diabetes is 51. However, the PD shared 45, 43 and 42 significantly expressed genes with the ageing, high dietary fat and high body fat respectively. The PD shared less than 40 significant transcripts with other factors. Ontological and pathway analyses have identified significant gene ontology and molecular pathways that enhance our understanding of the fundamental molecular procedure of the PD progression. Therapeutic targets of the PD could be developed using these identified target genes, ontologies and pathways. Our formulated methodologies demonstrate a network-based approach to understand the disease mechanism and the causative reason of the PD, and the identification for therapeutic targets of the PD.

neuroscience

Spatial structure increases the benefits of antibiotic production in Streptomyces griseus

Bacteria in the soil compete for limited resources to survive and proliferate. One of the ways they might do this is by producing antibiotics, but the costs of antibiotic production and their low concentrations in soils have led to uncertainty about the role of these natural products for the bacteria that produce them. Here, we examine the fitness effects of streptomycin production by the filamentous soil bacterium Streptomyces griseus and the conditions that modify its ability to invade competitors. Using pairwise competion assays, we first provide direct evidence that streptomycin production enables S. griseus to kill and invade a population of the susceptible species, S. coelicolor, but not a streptomycin-resistant mutant of this species. Next we show that the fitness benefits of streptomycin production are density-dependent, because production scales positively with cell number, and frequency-dependent, with a threshold of invasion of S. griseus at around 1%. Finally, using serial transfer experiments where spatial structure is either maintained or periodically destroyed, we show that spatial structure reduces the threshold frequency of invasion by more than 100-fold, indicating that antibiotic production can permit invasion from extreme rarity. Our results provide clear evidence that streptomycin is both an offensive and defensive weapon that facilitates invasion into occupied habitats and also protects against invasion by competitors. They also indicate that the benefits of antibiotic production rely on ecological interactions occurring at small local scales, suggesting that low antibiotic concentrations in bulk soil are unlikely to be representative of their effective concentrations in nature.

microbiology

Diversity Converges During Community Assembly In Methanogenic Granules, Suggesting A Biofilm Life-Cycle

Anaerobic biological decomposition of organic matter is ubiquitous in Nature wherever anaerobic environments prevail, and is catalysed by hydrolytic, fermentative, acetogenic, methanogenic, and various other groups, including syntrophic bacteria. It is also harnessed in innovative ways in engineered systems that may rely on small (0.1-4.0 mm), spherical, anaerobic granules, which we have found to be highly-replicated, whole-ecosystems harbouring the entire community necessary to mineralise complex organics. We hypothesised distinct granule sizes correspond to stages in a biofilm life-cycle, in which small granules are young and larger ones are old. Here, granules were separated into 10 size fractions used for physico-chemical and ecological characterisation. Gradients of volatile solids, density, settleability, biofilm morphology, methanogenic activity, and EPS profiles were observed across size fractions. Sequencing of 16S rRNA genes indicated linear convergence of diversity during community assembly as granules increased in size. A total of 155 discriminant OTUs were identified, and correlated strongly with physico-chemical parameters. Community assembly across sizes was influenced by a niche effect, whereby Euryarchaeota dominated a core microbiome presumably as granules became more anaerobic. The findings indicate opportunities for precision management of environmental biotechnologies, and the potential of aggregates as playgrounds to study assembly and succession in whole microbiomes.

microbiology

The role of African buffalo in the epidemiology of foot-and-mouth disease in sympatric cattle and buffalo populations in Kenya

Transmission of pathogens at wildlife-livestock interfaces poses a substantial challenge to the control of infectious diseases, including for foot-and-mouth disease virus (FMDV) in African buffalo and cattle. The extent to which buffalo play a role in the epidemiology of this virus in livestock populations remains unresolved in East Africa. Here, we show that FMDV occurs at high seroprevalence (~77%) in Kenyan buffalo. In addition, we recovered 80 FMDV VP1 sequences from buffalo, all of which were serotype SAT1 and SAT2, and seventeen FMDV VP1 sequences from cattle, which included serotypes A, O, SAT1 and SAT2. Notably, six individual buffalo were co-infected with both SAT1 and SAT2 serotypes. Our results suggest that transmission of FMDV between sympatric cattle and buffalo is rare. However, viruses from FMDV outbreaks in cattle elsewhere in Kenya were caused by viruses closely related to SAT1 and SAT2 viruses found in buffalo. We also show that the circulation of FMDV in buffalo is influenced by fine-scale geographic features, such as rivers, and that social segregation amongst sympatric herds may limit between-herd transmission. Our results significantly advance knowledge of the ecology and molecular epidemiology of FMDV at wildlife-livestock interfaces in Eastern Africa, and will help to inform the design of control and surveillance strategies for this disease in the region.

epidemiology

A phosphate starvation response gene (psr1-like) is present and expressed in Micromonas pusilla and other marine algae

Phosphorus (P) limits primary production in regions of the surface ocean, and many plankton species exhibit specific physiological responses to P-deficiency. The metabolic response of Micromonas pusilla, an ecologically relevant marine photoautotroph, to P-deficiency was investigated using environmental metabolomics and comparative genomics. The concentrations of some intracellular metabolites were elevated in the P-deficient cells (e.g., xanthine, inosine) and genes involved in the associated metabolic pathways shared a predicted conserved amino acid motif in the non-coding regions of each gene. The presence of the conserved motif suggests that these genes may be co-regulated, and the motif may constitute a regulatory element for binding a transcription factor, specifically that of Psr1 (Phosphate starvation response,), first described in the alga, Chlamydomonas reinhardtii. A putative phosphate starvation response gene (psr1-like) was identified in M. pusilla with homology to well characterized psr1/phr1 genes in algae and plants, respectively. This gene appears to be present and expressed in other marine algal taxa (e.g., Emiliania huxleyi) in field sites that are chronically phosphorus-limited. Results from the present study have implications for understanding phytoplankton taxon-specific roles in mediating P cycling in the ocean.

microbiology

Ancient DNA from chewing gums connects material culture and genetics of Mesolithic hunter-gatherers in Scandinavia

The discussion of an early postglacial dual-route colonization of the Scandinavian Peninsula is largely based on associating genomic data to an early dispersal of lithic technology from the East European Plain. However, a direct link between the two has been lacking. We tackle this problem by analysing human DNA from birch bark pitch mastics, \"chewing gums\", from Huseby Klev, a site in western Sweden with eastern lithic technology. We generate genome- wide data for three individuals, and show their affinity to the Scandinavian hunter-gatherers, or more precisely, to individuals from postglacial Sweden. Our samples date to 9880-9540 calBP, expanding the temporal range of this genetic group as well as its distribution. Human DNA from mastics provides a clear connection between material culture and genetic data. We also propose that DNA from different types of mastics can be used to study environment, ecology, and oral microbiome of prehistoric populations.

genomics